LESIONS OF THE LATERAL HYPOTHALAMUS IMPAIR THE PRESSOR-RESPONSE TO CLONIDINE INJECTED INTO THE MEDIAL SEPTAL AREA OF CONSCIOUS RATS

The central injection of clonidine (an alpha-2-adrenoceptor agonist) in conscious normotensive rats produces hypertensive responses and bradycardia. The present study was performed to investigate the effect of electrolytic lesions of the lateral hypothalamus (LH) on the pressor and bradycardic responses induced by clonidine injected into the medial septal area (MSA) in conscious and unrestrained rats. Male Holtzman rats weighing 250-300 g were used. Mean arterial pressure and heart rate were recorded in sham- or bilateral LH-lesioned rats with a cerebral stainless steel cannula implanted into the MSA. The injection of clonidine (40 nmol/mu-l) into the MSA of sham rats (N = 8) produced a pressor response (36 +/- 7 mmHg, P<0.05) and bradycardia (-70 +/- 13 bpm, P<0.05) compared to saline. Fourteen days after LH-lesion (N = 9) the pressor response was reduced (9 +/- 10 mmHg, P<0.05) but no change was observed in the bradycardia (-107 +/- 24 bpm). These results show that LH is an important area involved in the pressor response to clonidine injected into the MSA of rats.

AV3V LESION SUPPRESSES THE PRESSOR, DIPSOGENIC AND NATRIURETIC RESPONSES TO CHOLINERGIC ACTIVATION OF THE SEPTAL AREA IN RATS

In the present study we investigated the effect of anteroventral third ventricle (AV3V) lesion on pressor, dipsogenic, natriuretic and kaliuretic responses induced by the injection of carbachol (a cholinergic agonist) into the medial septal area (MSA) of rats. Male rats with sham or AV3V lesion and a stainless-steel cannula implanted into the MSA were used. Carbachol (2 nmol) injected into the MSA in sham lesion rats produced pressor (43 +/- 2 mmHg), dipsogenic (9.6 +/- 1.2 ml/h), natriuretic (531 +/- 82-mu-Eq/120 min) and kaliuretic (164 +/- 14-mu-Eq/120 min) responses. In AV3V-lesioned rats (1-5 days and 14-18 days), the pressor (11 +/- 2 mmHg, respectively), dipsogenic (1.9 +/- 0.7 and 1.4 +/- 0.6 ml/h), natriuretic (21 +/- 5 and 159 +/- 44-mu-Eq/120 min) and kaliuretic (124 +/- 14 and 86 +/- 13-mu-Eq/120 min) responses induced by carbachol injection into the MSA were reduced. These results show that the AV3V region is essential for the pressor, dipsogenic, natriuretic and kaliuretic responses induced by cholinergic activation of the MSA in rats.

Myosin heavy chain expression and atrophy in rat skeletal muscle during transition from cardiac hypertrophy to heart failure

The purpose of this investigation was to determine whether changes in myosin heavy chain (MHC) expression and atrophy in rat skeletal muscle are observed during transition from cardiac hypertrophy to chronic heart failure (CHF) induced by aortic stenosis (AS). AS and control animals were studied 12 and 18 weeks after surgery and when overt CHF had developed in AS animals, 28 weeks after the surgery. The following parameters were studied in the soleus muscle: muscle atrophy index (soleus weight/body weight), muscle fibre diameter and frequency and MHC expression. AS animals presented decreases in both MHC1 and type I fibres and increases in both MHC2a and type IIa fibres during late cardiac hypertrophy and CHF. Type IIa fibre atrophy occurred during CHF. In conclusion, our data demonstrate that skeletal muscle phenotype changes occur in both late cardiac hypertrophy and heart failure; this suggests that attention should be given to the fact that skeletal muscle phenotype changes occur prior to overt heart failure symptoms.

NOVEL EVIDENCE THAT BETA-ADRENOCEPTORS OF THE MEDIAL SEPTAL AREA REGULATE BLOOD-PRESSURE AND ELECTROLYTE BALANCE

We investigated the participation of the beta-adrenoceptors of the septal area (SA) in sodium and potassium excretion and urine flow. The alterations in arterial pressure and some renal functions were also investigated. The injection of 2.10(-9) to 16.10(-9)M of isoproterenol, through a cannula permanently implanted into the SA produced a significant dose-dependent decrease in urinary Na+ and K+ excretion and urinary flow. Pretreatment with 16.10(-9) M butoxamine antagonized the effect of 4.10(-9) M isoproterenol but pretreatment with 16.10(-9) M practolol did not abolish the effect of isoproterenol. The beta 2-agonist terbutaline and salbutamol (4.10(-9) M when injected intraseptally also caused a decrease in urine flow and in renal Na+ and K+ excretion. After injection of isoproterenol or salbutamol (4.10(-9) M) into the SA, the arterial pressure, glomerular, filtration rate (GFR) and filtered Nd were reduced while Na+ fractional reabsorption was increased. The results indicate that the beta 2-adrenoceptors of the SA play a role in the decrease of Na+, K+ and urine flow and this effect may be due to a drop in GFR and filtered Na+ and to the rise in tubular Na+ reabsorption.

ALPHA-ADRENERGIC PATHWAYS IN THE LATERAL HYPOTHALAMUS ARE IMPORTANT FOR THE DIPSOGENIC EFFECT OF CARBACHOL INJECTED INTO THE MEDIAL SEPTAL AREA

We studied the effect of the alpha(1)- and alpha(2)-adrenergic receptors of the lateral hypothalamus (LH) on the control of water intake induced by injection of carbachol into the medial septal area (MSA) of adult male Holtzman rats (250-300 g) implanted with chronic stainless steel cannulae into the LH and MSA. The volume of injection was always 1 mu l and was injected over a period of 30-60 s. For control, 0.15 M NaCl was used. Clonidine (20 nmol) but not phenylephrine (160 nmol) injected into the LH inhibited water intake induced by injection of carbachol (2 nmol) into the MSA, from 5.4 +/- 1.2 ml/h to 0.3 +/- 0.1 and 3.0 +/- 0.9 ml/h, respectively (N = 26). When we injected yohimbine (80 nmol) + clonidine (20 nmol) and prazosin (40 nmol) + clonidine (20 nmol) into theLH, water intake induced by injection of carbachol into the MSA was inhibited from 5.4 +/- 1.2 ml/h to 0.8 +/- 0.5 and 0.3 +/- 0.2 ml/h, respectively (N = 19). Water intake induced by carbachol (2 nmol) injected into the MSA was decreased by previous injection of yohimbine (80 nmol) + phenylephrine (160 nmol) and prazosin (40 nmol) + phenylephrine (l60 nmol) from 5.4 +/- 1.2 ml/h to 1.0 +/- 0.7 and 1.8 +/- 0.8 ml/h, respectively (N = 16). The cannula reached both the medial septal area in its medial portion and the lateral hypothalamus. It has been suggested that the different pathways for induction of drinking converge on a final common pathway. Thus, adrenergic stimulation of alpha(2),-adrenoceptors ofLH can influence this final common pathway.

Improved systolic ventricular function with normal myocardial mechanics in compensated cardiac hypertrophy

There is still controversy about the relation between changes in myocardial contractile function and global left ventricular (LV) performance during stable concentric hypertrophy. To clarify this, we analyzed LV function in vivo and myocardial mechanics in vitro in rats with pressure overload-induced cardiac hypertrophy. Male Wistar rats (70 g) Underwent ascending aortic stenosis for 8 weeks (group AAS, n = 9). LV performance wits assessed by transthoracic echocardiography Under anesthesia. Myocardial function Was studied in isolated papillary muscle preparations during isometric contraction. The data were compared with age- and sex-matched sham-operated rats (group C, 11 = 9). LV weight-to-body weight ratio (C: 2.13 +/- 0.14 mg/g; AAS: 3.24 +/- 0.44) LV relative wall thickness (C: 0.18 +/- 0.02; AAS: 0.33 +/- 0.09), and LV fractional shortening (C: 54 +/- 5%; AAS: 70 +/- 8%) were increased in group AAS (P<0.05). Echocardio-graphic analysis also indicated a significant association (r = 0.74 P<0.001) between the percent fractional shortening index and LV relative wall thickness. The performance of AAS isolated In muscle revealed that active tension (C: 6.6 +/- 1.7 g/mm(2); AAS: 6.5 +/- 1.5 g/mm(2)) and maximum rate of tension development (C: 69 +/- 21 g/mm(2)/s AAS: 69 +/- 18 g/mm(2)/s) were not significantly different Front group C (P>0.05). In conclusion, compensated pressure-overload myocardial hypertrophy is associated with preserved myocardial function and increased ventricular performance. The improved LV function might be due to the ventricular remodeling, characterized by an increased relative wall thickness.