Effects of small doses of ouabain on the arterial blood pressure of anesthetized hypertensive and normotensive rats

Ouabain increases vascular resistance and may induce hypertension by inhibiting the Na+ pump. The effects of 0.18 and 18 µg/kg, and 1.8 mg/kg ouabain pretreatment on the phenylephrine (PHE; 0.1, 0.25 and 0.5 µg, in bolus)-evoked pressor responses were investigated using anesthetized normotensive (control and uninephrectomized) and hypertensive (1K1C and DOCA-salt treated) rats. Treatment with 18 µg/kg ouabain increased systolic and diastolic blood pressure in all groups studied. However, the magnitude of this increase was larger for the hypertensive 1K1C and DOCA-salt rats than for normotensive animals, while the pressor effect of 0.18 µg/kg ouabain was greater only in DOCA-salt rats. A very large dose (1.8 mg/kg) produced toxic effects on the normotensive control but not on uninephrectomized or 1K1C rats. Rat tail vascular beds were perfused to analyze the effects of 10 nM ouabain on the pressor response to PHE. In all animals, 10 nM ouabain increased the PHE pressor response, but this increase was larger in hypertensive DOCA-salt rats than in normotensive and 1K1C rats. Results suggested that a) increases in diastolic blood pressure induced by 18 µg/kg ouabain were larger in hypertensive than normotensive rats; b) in DOCA-salt rats, smaller ouabain doses had a stronger effect than in other groups; c) hypertensive and uninephrectomized rats were less sensitive to toxic doses of ouabain, and d) after treatment with 10 nM ouabain isolated tail vascular beds from DOCA-salt rats were more sensitive to the pressor effect of PHE than those from normotensive and 1K1C hypertensive rats. These data suggest that very small doses of ouabain, which might produce nanomolar plasma concentrations, enhance pressor reactivity in DOCA-salt hypertensive rats, supporting the idea that endogenous ouabain may contribute to the increase and maintenance of vascular tone in hypertension.

Arterial blood pressure of term newborns during the first week of life

The progressive behavior of the blood pressure of term newborns during the first week of life was assessed by the simultaneous use of oscillometric and Doppler methods. A total of 174 term neonates born at the Municipal Hospital Odilon Behrens in Belo Horizonte, from March 1996 to February 1997, were prospectively assessed. The oscillometric and Doppler ultrasonic methods were simultaneously used for four consecutive recordings obtained at 12 ± 6, 24 ± 6 and 72 ± 24 h and on the 7th ± 1 day of life. The combined use of the two methods simplified the procedure, with automatic cuff inflation and deflation, and speed was properly controlled with an automatic pressure monitor. The procedure was performed using a Y-connection to the mercury sphygmomanometer, with blood pressure being recorded with an automatic device and systolic blood pressure being measured simultaneously by Doppler ultrasound. The newborns were awake, not crying and in the supine position. A statistically significant increase in systolic and diastolic blood pressure was observed between the first and second, and the third and fourth measurements by Doppler and oscillometric methods. No significant correlation between birth weight, length, ponderal index and blood pressure was observed. The technique used represents a simpler and more accurate procedure for blood pressure measurement.

Response of the arterial blood pressure of quadriplegic patients to treadmill gait training

Blood pressure pattern was analyzed in 12 complete quadriplegics with chronic lesions after three months of treadmill gait training. Before training, blood pressure values were obtained at rest, during treadmill walking and during the recovery phase. Gait training was performed for 20 min twice a week for three months. Treadmill gait was achieved using neuromuscular electrical stimulation, assisted by partial body weight relief (30-50%). After training, blood pressure was evaluated at rest, during gait and during recovery phase. Before and after training, mean systolic blood pressures and heart rates increased significantly during gait compared to rest (94.16 ± 5.15 to 105 ± 5.22 mmHg and 74.27 ± 10.09 to 106.23 ± 17.31 bpm, respectively), and blood pressure decreased significantly in the recovery phase (86.66 ± 9.84 and 57.5 ± 8.66 mmHg, respectively). After three months of training, systolic blood pressure became higher at rest (94.16 ± 5.15 mmHg before training and 100 ± 8.52 mmHg after training; P < 0.05) and during gait exercise (105 ± 5.22 mmHg before and 110 ± 7.38 mmHg after training; P < 0.05) when compared to the initial values, with no changes in heart rate. No changes occurred in blood pressure during the recovery phase, with the lower values being maintained. A drop in systolic pressure from 105 ± 5.22 to 86.66 ± 9.84 mmHg before training and from 110 ± 7.38 to 90 ± 7.38 mmHg after training was noticed immediately after exercise, thus resulting in hypotensive symptoms when chronic quadriplegics reach the sitting position from the upright position.

Effects of metformin on the glycemic control, lipid profile, and arterial blood pressure of type 2 diabetic patients with metabolic syndrome already on insulin

Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI), waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001) after the addition of metformin (1404.4 ± 565.5 mg/day), with 14% of the 57 patients reaching A1C levels up to 7%, and 53% reaching values up to 8%. There was a statistically significant reduction (P < 0.05) of total cholesterol (229.0 ± 29.5 to 214.2 ± 25.0 mg/dL), BMI (30.7 ± 5.4 to 29.0 ± 4.0 kg/m²), waist circumference (124.6 ± 11.7 to 117.3 ± 9.3 cm), and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 ± 1.03 to 8.18 ± 1.01%) and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002). INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

Long-term facial artery catheter implantation for serial arterial blood sampling and invasive arterial blood pressure measurement in horses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Interaction between supraoptic nucleus and septal area in the control of water, sodium intake and arterial blood pressure induced by injection of angiotensin II

We investigated the effects of injection into the supraoptic nucleus (SON) of losartanand PD 123319 (nonpeptide AT(1) and AT(2)- angiotensin II [ANG II] receptor antagonists, respectively); d(CH2)(5)-Tyr(Me)-AVP (AVPA; an arginine-vasopressin [AVP] V-1 receptor antagonist), FK 409 (a nitric oxide [NO] donor), and N-W-mtro-(L)-arginine methyl ester ((L)-NAME; an NO synthase inhibitor) oil water intake, sodium chloride 3% (NaCl) intake and arterial blood pressure induced by injection of ANG 11 into the lateral septal area (LSA). Mate Holtzman rats (250-300 g) were implanted with cannulae into SON and LSA unilaterally. The drugs were injected in 0.5 mul over 30-60 s. Controls were injected with a similar volume of 0.15 M NaCl. ANG II was injected at a dose of 10 pmol. ANG II antagonists and AVPA were injected at doses of 80 nmol. FK 409 and (L)-NAME were injected at doses of 20 and 40 mug, respectively. Water and NaCl intake was measured over a 2-h period. Prior administration of losartan into the SON decreased water and NaCl intake induced by injection of ANG II. While there was a decrease in water intake, ANG II-induced NaCl intake was significantly increased following injection of AVPA. FK 409 injection decreased water intake and sodium intake induced by ANG II. L-NAME alone increased water and sodium intake and induced a pressor effect. (L)-NAME-potentiated water and sodium intake induced by ANG II. PD 123319 produced no changes in water or sodium intake induced by ANG II. The prior administration of losartan or AVPA decreased mean arterial pressure (MAP) induced by ANG II. PD 123319 decreased the pressor effect of ANG II to a lesser degree than losartan. FK 409 decreased the pressor effect of ANG II while (L)-NAME potentiated it. These results suggest that both ANG II AT, and AVP V, receptors and NO within the SON may be involved in water intake, NaCl intake and the pressor response were induced by activation of ANG II receptors within the LSA. These results do not support the involvement of LSA AT(2) receptors in the mediation of water and NaCl intake responses induced by ANG II, but influence the pressor response. (C) 2004 Elsevier B.V. All rights reserved.

Nitric oxide of the supraoptic nucleus influences the salivary secretion, sodium renal excretion, urinary volume and arterial blood pressure induced by pilocarpine

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125.0 mg and zolazepan chloridrate 125.0 mg) into quadriceps muscle and stainless steel cannulas were implanted into their supraoptic nucleus (SON). We investigated the effects of the injection into the supraoptic nucleus (SON) of FK 409, a nitric oxide donor, and N(W-)nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor (NOS), on the salivary secretion, arterial blood pressure, sodium excretion and urinary volume induced by pilocarpine, which was injected into SON. The drugs were injected in 0.5 mul volume over 30-60 s. Controls was injected with a similar volume of 0.15 M NaCl. FK 409 and L-NAME were injected at doses of 20 mug/0.5 mul and 40 mug/0.5 mul. respectively. The amount of saliva secretion was studied over a five-minute period after injection of pilocarpine into SON. Injection of pilocarpine (10, 20, 40, 80, 160 mug/mul) into SON produced a dose-dependent increase in salivary secretion. L-NAME was injected into SON prior to the injection of pilocarpine into SON, producing an increase in salivary secretion due to the effect of pilocarpine. FK 409 injected into SON attenuating the increase in salivary secretion induced by pilocarpine. Mean arterial pressure (MAP) increase after injections of pilocarpine into the SON. L-NAME injected into the SON prior to injection of pilocarpine into SON increased the MAP. FK 409 injected into the SON prior to pilocarpine attenuated the effect of pilocarpine on MAP. Pilocarpine (0.5 mumol/0.5 mul) injected into the SON induced an increase in sodium and urinary excretion. L-NAME injected prior to pilocarpine into the SON increased the urinary sodium excretion and urinary volume induced by pilocarpine. FK 409 injected prior to pilocarpine into the SON decreased the sodium excretion and urinary volume induced by pilocarpine. All these roles of pilocarpine depend on the release of nitric oxide into the SON. In summary the present results show: a) SON is involved in pilocarpine-induced salivation; b) that mechanism involves increase in MAP, sodium excretion and urinary volume. (C) 2003 Elsevier B.V. All rights reserved.

Lateral hypothalamus lesions influences water and salt intake, and sodium and urine excretion, and arterial blood pressure induced by L-NAME and FK 409 injections into median preoptic nucleus in conscious rats

Male Holtzman rats weighting 200-250 g were anesthetized with zoletil 50 mg/Kg (tiletamine chloridrate 125,0 mg and zolazepan chloridrate 125,0 mg) into quadriceps muscle and submitted an electrolytic lesion of the lateral hypothalamus (LH) and a stainless steel cannula was implanted into their median preoptic nucleus (MnPO). We investigated the effects of the injection into the (MnPO) of FK 409 (20 mug/0.5 mul), a nitric oxide (NO) donor, and N-W-nitro-L-arginine methyl ester (L-NAME) 40 mug/0.5 mul, a nitric oxide synthase inhibitor (NOSI), on the water and sodium appetite and the natriuretic, diuretic and cardiovascular effects induced by injection of L-NAME and FK 409 injected into MnPO in rats with LH lesions. Controls were injected with a similar volume of 0.15 M NaCl. L-NAME injected into MnPO produced an increase in water and sodium intake and in sodium and urine excretion and increase de mean arterial pressure (MAP). FK 409 injected into MnPO did not produce any change in the hydro electrolytic and cardiovascular parameters in LH-sham and lesioned rats. FK 409 injected before L-NAME attenuated its effects. These data show that electrolytic lesion of the LH reduces fluid and sodium intake as well as sodium and urine excretion, and the pressor effect induced by L-NAME. LH involvement with NO of the MnPO excitatory and inhibitory mechanisms related to water and sodium intake, sodium excretion and cardiovascular control is suggested. (C) 2004 Elsevier B.V. All rights reserved.

Nitric oxide and L-type calcium channel influences the changes in arterial blood pressure and heart rate induced by central angiotesin II

We study the voltage dependent calcium channels and nitric oxide involvement in angiotensin II-induced pressor effect. The antipressor action of L-Type calcium channel antagonist, nifedipine, has been studied when it was injected into the third ventricle prior to angiotensin II. The influence of nitric oxide on nifedipine antipressor action has also been studied by utilizing N(W)-nitro-L-arginine methyl ester (LNAME) (40 mu g/0.2 mu l) a nitric oxide synthase inhibitor and L-arginine ( 20 mu g/0.2 mu l), a nitric oxide donor agent. Adult male Holtzman rats weighting 200-250 g, with cannulae implanted into the third ventricle were injected with angiotensin II. Angiotensin II produced an elevation in mean arterial pressure and a decreased in heart rate. Such effects were potentiated by the prior injection of LNAME. L-arginine and nifedipine blocked the effects of angiotensin II. These data showed the involvement of L-Type calcium channel and a free radical gas nitric oxide in the central control of angiotensin II-induced pressor effect. This suggested that L-Type calcium channel of the circunventricular structures of central nervous system participated in both short and long term neuronal actions of ANG II with the influence of nitrergic system.

Influence of arginine vasopressin receptors and angiotensin receptor subtypes on the water intake and arterial blood pressure induced by vasopressin injected into the lateral septal area of the rat

In this study we investigated the influence of d(CH2)(5)-Tyr(Me)-[Arg(8)]vasopressin (AAVP) and [adamanteanacetyl(1),0-ET-DTyr(2), Val(4), aminobutyryl(6), Arg(8,9)]-[Arg(8)]vasopressin (ATAVP), which are antagonists of vasopressin V-1 and V-2 receptors, and the effects of losartan, a selective angiotensin AT(1) receptor antagonist, and CGP42112A, a selective AT(2) receptor antagonist, injected into the lateral septal area (LSA) on thirst and hypertension induced by [Arg(8)]vasopressin (AVP). AAVP and ATAVP injected into the LSA reduced the drinking responses elicited by injecting AVP into the LSA. Both the AT(1) and AT(2) ligands administered into the LSA elicited a concentration-dependent decrease in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A. The increase in MAP, due to injection of AVP into the LSA, was reduced by prior injection of AAVP from 18 +/- 1 to 6 +/- 1 mm Hg. Losartan injected into the LSA prior to AVP reduced the increase in MAP to 7 +/- 0.8 mm Hg. ATAVP and CGP42112A produced no changes in the pressor effect of AVP. These results suggest that the dipsogenic effects induced by injecting AVP into the LSA were mediated primarily by AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple AVP and angiotensin II receptor subtypes. The pressor response of AVP was reduced by losartan and by AAVP. CGP42112A and ATAVP did not change the AVP pressor response. These results suggest that facilitator effects of AVP on water intake are mediated through the activation of V-1 receptors and that the inhibitory effect requires V-2 receptors. The involvement of AT(1) and AT(2) receptors can be postulated. Based on the present findings, we suggest that the AVP in the LSA may play a role in the control of water and arterial blood pressure balance. (C) 2004 Elsevier B.V. All rights reserved.