Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1) progressively increased arterial pressure from 108 ± 6.0 to 149 ± 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 ± 18 to 222 ± 59 µl min-1 100 g body weight-1 (P<0.05) and a rise in fractional urinary sodium excretion from 0.2 ± 0.04 to 1.62 ± 0.35% (P<0.05) and in sodium post-proximal fractional excretion from 0.54 ± 0.09 to 4.7 ± 0.86% (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 ± 0.04 to 4.5 ± 1.6% and from 0.1 ± 0.015 to 1.21 ± 0.37%, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the post-proximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity.

Familial predisposition to hypertension and the association between urinary sodium excretion and blood pressure in a population-based sample of young adults

The reasons for the inconsistent association between salt consumption and blood pressure levels observed in within-society surveys are not known. A total of 157 normotensive subjects aged 18 to 35 years, selected at random in a cross-sectional population-based survey, answered a structured questionnaire. They were classified as strongly predisposed to hypertension when two or more first-degree relatives had a diagnosis of hypertension. Anthropometric parameters were obtained and sitting blood pressure was determined with aneroid sphygmomanometers. Sodium and potassium excretion was measured by flame spectrophotometry in an overnight urine sample. A positive correlation between blood pressure and urinary sodium excretion was detected only in the group of individuals strongly predisposed to hypertension, both for systolic blood pressure (r = 0.51, P<0.01) and diastolic blood pressure (r = 0.50, P<0.01). In a covariance analysis, after controlling for age, skin color and body mass index, individuals strongly predisposed to hypertension who excreted amounts of sodium above the median of the entire sample had higher systolic and diastolic blood pressure than subjects classified into the remaining conditions. The influence of familial predisposition to hypertension on the association between salt intake and blood pressure may be an additional explanation for the weak association between urinary sodium excretion and blood pressure observed in within-population studies, since it can influence the association between salt consumption and blood pressure in some but not all inhabitants.

Influence of a multideficient diet from northeastern Brazil on resting blood pressure and baroreflex sensitivity in conscious, freely moving rats

The "regional basic diet" or RBD is a multideficient diet (providing 8% protein) which is known to produce dietary deficiencies in some populations in northeastern Brazil. The present study investigated the effects of RBD-induced malnutrition on resting blood pressure and baroreflex sensitivity in conscious rats. Malnourished rats were obtained by feeding dams the RBD during mating and pregnancy (RBD-1 group) or during nursing and a 10-day period after weaning (RBD-2 group). At 90 days of age, only RBD-2 rats weighed significantly (P<0.001) less than control rats born to dams fed a standard commercial diet (23% protein) during pregnancy and nursing. Baseline mean arterial pressure and heart rate of both RBD-1 and RBD-2 rats were comparable to those of controls. The slopes for both reflex bradycardia and tachycardia (bpm/mmHg) induced by intravenous phenylephrine and sodium nitroprusside, respectively, were unchanged in either RBD-1 (-2.08 ± 0.11 and -3.10 ± 0.43, respectively) or RBD-2 (-2.32 ± 0.30 and -3.73 ± 0.53, respectively) rats, when compared to controls (-2.09 ± 0.10 and -3.17 ± 0.33, respectively). This study shows that, after a prolonged period of nutritional recovery, the patterns of resting blood pressure and baroreflex sensitivity of both pre- and postnatally malnourished rats were similar to those of controls. The decreased body weight and the tendency to increased reflex tachycardia in RBD-2 rats may suggest that this type of maternal malnutrition during lactation is more critical than during pregnancy.

Oral administration of L-arginine decreases blood pressure and increases renal excretion of sodium and water in renovascular hypertensive rats

The two-kidney, one-clip renovascular (2K1C) hypertension model is characterized by a reduction in renal flow on the clipped artery that activates the renin-angiotensin system. Endothelium dysfunction, including diminished nitric oxide production, is also believed to play a role in the pathophysiology of this model. Some studies have shown an effect of L-arginine (L-Arg, a nitric oxide precursor) on hypertension. In the present study we determined the ability of L-Arg (7 days of treatment) to reduce blood pressure and alter renal excretions of water, Na+ and K+ in a model of 2K1C-induced hypertension. Under ether anesthesia, male Wistar rats (150-170 g) had a silver clip (0.20 mm) placed around the left renal artery to produce the 2K1C renovascular hypertension model. In the experimental group, the drinking water was replaced with an L-Arg solution (10 mg/ml; average intake of 300 mg/day) from the 7th to the 14th day after surgery. Sham-operated rats were used as controls. At the end of the treatment period, mean blood pressure was measured in conscious animals. The animals were then killed and the kidneys were removed and weighed. There was a significant reduction of mean blood pressure in the L-Arg-treated group when compared to control (129 ± 7 vs 168 ± 6 mmHg, N = 8-10 per group; P<0.05). Concomitantly, a significant enhancement of water and Na+ excretion was observed in the 2K1C L-Arg-treated group when compared to control (water: 13.0 ± 0.7 vs 9.2 ± 0.5 ml/day, P<0.01; Na+: 1.1 ± 0.05 vs 0.8 ± 0.05 mEq/day, respectively, P<0.01). These results show that orally administered L-Arg acts on the kidney, possibly inducing changes in renal hemodynamics or tubular transport due to an increase in nitric oxide formation.

Therapeutic approach to patients complaining of high blood pressure in a cardiological emergency room

OBJECTIVE: To evaluate the management of patients complaining of high blood pressure (BP) in a cardiological emergency room. METHODS: Patients referred to the cardiological emergency room with the main complaint of high blood pressure were consecutively selected. The prescriptions and the choice of antihypertensive drugs were assessed. The classification of these patients as hypertensive emergencies or pseudoemergencies, according to the physician who provided initial care, was recorded. RESULTS: From a total of 858 patients presenting to the emergency room, 80 (9.3%) complained of high BP, and 61 (76.3%) received antihypertensive drugs. Sublingual nifedipine was the most commonly used drug (59%). One patient received intravenous medication, one patient was hospitalized and 6 patients (7.5%) were classified as hypertensive emergencies or pseudoemergencies. CONCLUSION: High BP could seldom be classified as a hypertensive emergency or pseudoemergency, even though it was a frequent complaint (9.3% of visits). Currently, the therapeutic approach is not recommended, even in specialized clinics.

Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring

OBJECTIVE: A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. METHODS: Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups. RESULTS: Significant reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. CONCLUSION: Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trandolapril during treatment of mild-to-moderate essential systemic hypertension.

Laboratory assessment of the hypertensive individual. Value of the main guidelines for high blood pressure

OBJECTIVE: To determine if abnormal laboratory findings are more common in individuals with hypertension and in those with other risk factors, such as obesity, smoking and alcohol ingestion. METHODS: A study was carried out in the general outpatient clinics of a university hospital (145 individuals without previous diagnosis of hypertension) and the following variables were assessed: high blood pressure (as defined by the VI Joint National Committee on Prevention, Detection and Treatment of High Blood Pressure - VI JNC), obesity [calculated using body mass index (BMI)], tobacco use, and alcoholic ingestion. The laboratory examinations consisted of the following tests: hemogram, glycemia, uric acid, potassium, total/HDL-fraction cholesterol, triglycerides, calcium and creatinine. RESULTS: High blood pressure was not associated with a higher number of abnormal laboratory tests. Hypertensive individuals with a BMI > or = 25kg/m² or normotensive obese individuals, however, had a higher frequency of diabetes (12X), hypertriglyceridemia (3X), and hypercholesterolemia (2X), as compared with hypertensive individuals with BMI <25kg/m² and preobese/normal weight normotensive individuals. CONCLUSION: High blood pressure is not associated with a higher frequency of abnormal laboratory tests. The association of high blood pressure and obesity, however, increases the detection of diabetes and dyslipidemias.

The effect of siesta in parameters of cardiac structure and in interpretation of ambulatory arterial blood pressure monitoring

OBJECTIVE: To evaluate the influence of the siesta in ambulatory blood pressure (BP) monitoring and in cardiac structure parameters. METHODS: 1940 ambulatory arterial blood pressure monitoring tests were analyzed (Spacelabs 90207, 15/15 minutes from 7:00 to 22:00 hours and 20/20 minutes from 22:01 to 6.59hours) and 21% of the records indicated that the person had taken a siesta (263 woman, 52±14 years). The average duration of the siesta was 118±58 minutes. RESULTS: (average ± standard deviation) The average of systolic/diastolic pressures during wakefulness, including the napping period, was less than the average for the period not including the siesta (138±16/85±11 vs 139±16/86±11 mmHg, p<0.05); 2) pressure loads during wakefulness including the siesta, were less than those observed without the siesta); 3) the averages of nocturnal sleep blood pressures were similar to those of the siesta, 4) nocturnal sleep pressure drops were similar to those in the siesta including wakefulness with and without the siesta; 5) the averages of BP in men were higher (p<0.05) during wakefulness with and without the siesta, during the siesta and nocturnal sleep in relation to the average obtained in women; 6) patients with a reduction of 0- 5% during the siesta had thickening of the interventricular septum and a larger posterior wall than those with a reduction during the siesta >5%. CONCLUSION: The siesta influenced the heart structure parameters and from a statistical point of view the average of systolic and diastolic pressures and the respective pressure loads of the wakeful period.

End-systolic pressure-diameter relation of the left ventricle during transient and sustained elevations of blood pressure

OBJECTIVE: To assess the effect of transient and sustained variations in cardiac load on the values of the end-systolic pressure-diameter relation (ESPDR) of the left ventricle. METHODS: We studied 13 dogs under general anesthesia and autonomic blockade. Variations of cardiac loads were done by elevation of blood pressure by mechanical constriction of the aorta. Two protocols were used in each animal: gradual peaking and decreasing pressure variation, the "transient arterial hypertension protocol" (TAH), and a quick and 10 min sustained elevation, the "sustained arterial hypertension protocol"(SAH). Then, we compared the ESDR in these two situations. RESULTS: Acute elevation of arterial pressure, being it "transitory" or "sustained", did not alter the heart frequency and increased similarly the preload and after load. However, they acted differently in end systolic pressure-diameter relation. It was greater in the SAH than TAH protocol, 21.0±7.3mmHg/mm vs. 9.2±1.2mmHg/mm (p<0.05). CONCLUSION: The left ventricular ESPDR values determined during sustained pressure elevations were higher than those found during transient pressure elevations. The time-dependent activation of myocardial contractility associated with the Frank-Starling mechanism is the major factor in inotropic stimulation during sustained elevations of blood pressure, determining an increase in the ESPDR values.

Response of blood pressure to maximum exercise in hypertensive patients under different therapeutic programs

OBJECTIVE: To evaluate the behavior of blood pressure during exercise in patients with hypertension controlled by frontline antihypertension drugs. METHODS: From 979ergometric tests we retrospectively selected 49 hipertensive patients (19 males). The age was 53±12 years old and normal range rest arterial pressure (<=140/90 mmHg) all on pharmacological monotherapy. There were 12 on beta blockers; 14 on calcium antagonists, 13 on diuretics and 10 on angiotensin converting enzyme inhibitor. Abnormal exercise behhavior of blood pressure was diagnosed if anyone of the following criteria was detected: peak systolic pressure above 220 mmHg, raising of systolic pressure > or = 10 mmHg/MET; or increase of diastolic pressure greater than 15 mmHg. RESULTS: Physiologic response of arterial blood pressure occurred in 50% of patients on beta blockers, the best one (p<0.05), in 36% and 31% on calcium antagonists and on diuretics, respectively, and in 20% on angiotensin converting enzyme inhibitor, the later the leastr one (p<0.05). CONCLUSION: Beta-blockers were more effective than calcium antagonists, diuretics and angiotensin-converting enzyme inhibitors in controlling blood pressure during exercise, and angiotensin converting enzyme inhibitors the least effective drugs.

Reduction in diastolic blood pressure and cardiovascular mortality in nondiabetic hypertensive patients. A reanalysis of the HOT study

OBJECTIVE: To use published Hypertension Optimal Treatment (HOT) Study data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure. METHODS: In the HOT Study, 18,700 patients from various centers were allocated at random to groups having different objectives of for diastolic blood pressure: <=90 (n=6264); <=85 (n=6264); <=80mmHg (n=6262). Felodipine was the basic drug used. Other antihypertensive drugs were administered in a sequential manner, aiming at the objectives of diastolic blood pressure reduction. RESULTS: The group of nondiabetic hypertensive subjects with diastolic pressure<=80mmHg had a cardiovascular mortality ratio of 4.1/1000 patients/year, 35.5% higher than the group with diastolic pressure <=90mmHg (cardiovascular mortality ratio, 3.1/1000 patients/year). In contrast, diabetic patients allocated to the diastolic pressure objective group of <=80mmHg had a 66.7% reduction in cardiovascular mortality (3.7/1000 patients/year) when compared with the diastolic pressure group of <=90mmHg (cardiovascular mortality ratio, 11.1/1000 patients/year). CONCLUSION: The results indicate that in hypertensive diabetic patients reduction in diastolic blood pressure to levels <=80mmHg decreases the risk of fatal cardiovascular events. It remains necessary to define the level of diastolic blood pressure <=90mmHg at which maximal reduction in cardiovascular mortality is obtained for nondiabetics.

Use of oral antihypertensive medication preceding blood pressure elevation in hospitalized patients

OBJECTIVE: To evaluate the frequency of oral antihypertensive medication preceding the increase in blood pressure in patients in a university hospital, the drug of choice, and the maintained use of antihypertensive medication. METHODS: Data from January to June 1997 from the University Hospital Professor Edgard Santos Pharmacy concerning the prescriptions of all inpatients were used. Variables included in the analysis were: antihypertensive medication prescription preceding increase in blood pressure, type of antihypertensive medication, gender, clinical or surgical wards, and the presence of maintained antihypertensive medication. RESULTS: The hospital admitted 2,532 patients, 1,468 in surgical wards and 818 in medical wards. Antihypertensive medication prescription preceding pressure increase was observed in 578 patients (22.8%). Nifedipine was used in 553 (95.7%) and captopril in 25 (4.3%). In 50.7% of patients, prescription of antihypertensive medication was not associated with maintained antihypertensive medication. Prescription of antihypertensive drugs preceding elevation of blood pressure was significantly (p<0.001) more frequent on the surgical floor (27.5%; 405/1468) than on the medical floor (14.3%; 117/818). The frequency of prescription of antihypertensive drugs preceding elevation of blood pressure without maintained antihypertensive drugs and the ratio between the number of prescriptions of nifedipine and captopril were greater in surgical wards. CONCLUSION: The use of antihypertensive medication, preceding elevation of blood pressure (22.8%) observed in admitted patients is not supported by scientific evidence. The high frequency of this practice may be even greater in nonuniversity hospitals.

Epworth's sleepiness scale in outpatients with different values of arterial blood pressure

OBJECTIVE: To compare sleepiness scores of the Epworth scale in patients with different levels of arterial pressure when undergoing outpatient monitoring within the context of clinical evaluation. METHODS: A total of 157 patients selected for outpatient monitoring of arterial pressure during hypertension evaluation were divided into 3 groups: group 1 - normotensive; group 2 - hypertensive; group 3 - resistant hypertensive. For analysis, values > or = 11 were considered as associated with respiratory disturbances during sleep. RESULTS: Seventeen (10.8%) patients in group 1, 112 (71.3%) in group 2, and 28 (17.8%) in group 3, which was composed of aged, more severely hypertensive individuals, were analyzed. Groups were similar relative to sex and body mass index, but different in relation to systolic and diastolic pressure levels and age. Despite an absolute difference, no statistically significant difference occurred between Epworth scores and in the proportion of patients with values > or = 11 (5.9% vs. 18.8% vs. 212.4%; P=0.37). Despite the positive association between degree of sleepiness measured with the scale and the severity of the hypertension, no statistical significance occurred following control by age (p=0.18). CONCLUSION: A positive correlation exists between degree of sleepiness and hypertension severity. The absence of a statistical significance shown in the present study could be due to a beta type of error. Instruments that render this complaint into an objective finding could help in the pursuit of an investigation of respiratory disturbances during sleep in more severely hypertensive patients, and should therefore be studied better.

Ambulatory blood pressure monitoring of patients with heart failure: a new prognosis marker

OBJECTIVE: To evaluate the relationship between 24-hour ambulatory arterial blood pressure monitoring and the prognosis of patients with advanced congestive heart failure. METHODS: We studied 38 patients with NYHA functional class IV congestive heart failure, and analyzed left ventricular ejection fraction, diastolic diameter, and ambulatory blood pressure monitoring data. RESULTS: Twelve deaths occurred. Left ventricular ejection fraction (35.2±7.3%) and diastolic diameter (72.2±7.8mm) were not correlated with the survival. The mean 24-hour (SBP24), waking (SBPw), and sleeping (SBPs) systolic pressures of the living patients were higher than those of the deceased patients and were significant for predicting survival. Patients with mean SBP24, SBPv, and SBPs > or = 105mmHg had longer survival (p=0.002, p=0.01 and p=0.0007, respectively). Patients with diastolic blood pressure sleep decrements (dip) and patients with mean blood pressure dip <=6mmHg had longer survival (p=0.04 and p=0.01, respectively). In the multivariate analysis, SBPs was the only variable with an odds ratio of 7.61 (CI: 1.56; 3704) (p=0.01). Patients with mean SBP<105mmHg were 7.6 times more likely to die than those with SBP > or = 105 mmHg CONCLUSION: Ambulatory blood pressure monitoring appears to be a useful method for evaluating patients with congestive heart failure.

Influence of Quality of Sleep on the Nocturnal Decline in Blood Pressure During Ambulatory Blood Pressure Monitoring

OBJECTIVE: To assess the influence of the quality of sleep on the nocturnal physiological drop in blood pressure during ambulatory blood pressure monitoring. METHODS: We consecutively assessed ambulatory blood pressure monitoring, the degree of tolerance for the examination, and the quality of sleep in 168 patients with hypertension or with the suspected "white-coat" effect. Blood pressure fall during sleep associated with a specific questionnaire and an analogical visual scale of tolerance for ambulatory blood pressure monitoring were used to assess usual sleep and sleep on the day of examination. Two specialists in sleep disturbances classified the patients into 2 groups: those with normal sleep and those with abnormal sleep. RESULTS: Fifty-nine (35 %) patients comprised the abnormal sleep group. Findings regarding the quality of sleep on the day of ambulatory blood pressure monitoring as compared with those regarding the quality of sleep on a usual day were different and were as follows, respectively: total duration of sleep (-12.4±4.7 versus -42.2±14.9 minutes, P=0.02), latency of sleep (0.4±2.7 versus 17±5.1 minutes, P<0.001), number of awakenings (0.1±0.1 versus 1.35±0.3 times, P<0.001), and tolerance for ambulatory blood pressure monitoring (8±0.2 versus 6.7±0.35, P=0.035). An abnormal drop in blood pressure during sleep occurred in 20 (18%) patients in the normal sleep group and in 14 (24%) patients in the abnormal sleep group, P=0.53. CONCLUSION: Ambulatory blood pressure monitoring causes sleep disturbances in some patients, and a positive association between quality of sleep and tolerance for the examination was observed.