Experiments were performed in male Wistar rats with renovascular hypertension (167 +/- 4.2 mmHg) produced by clipping the renal artery for a 3-wk period (2-kidney, 1-clip Goldblatt). The results were compared with those obtained in age-matched normotensive controls. Hypertension of 3-wk duration elicited a significant increase in ventricular weight (1.01 +/- 0.02 g) with respect to the controls (0.82 +/- 0.01 g) but had no significant effect on body weight. The inotropic responsiveness to beta-adrenergic stimulation was diminished in papillary muscles from renal hypertensive rats: the maximum increase in the maximal rate of rise of tension produced by isoproterenol was 27.39 +/- 5.4 and 11.77 +/- 2.91 g X mm-2 X s-1 (P less than 0.05) in control and hypertensive animals, respectively. Similar results were obtained when the estimated maximal velocity of shortening of the contractile element (Vmax) was used to assess myocardial contractility. The inotropic response to CaCl2 was also significantly depressed in the 2-kidney, 1-clip rats. However, the relaxant and the chronotropic responses to isoproterenol were not significantly modified in the Goldblatt rats. Assays of beta-adrenergic receptors to l-[3H]dihydroalprenolol binding, showed no significant changes in the number (expressed per mg of membrane protein) or in the affinity of the beta-receptors. These results suggest that at an early stage of the renal hypertensive model the impaired inotropic response to isoproterenol is not mediated by an alteration of the beta-receptors and should be searched at a postreceptor adenyl cyclase level.

Sodium homeostasis exerts a powerful influence on the cardiovascular system in normotensive and hypertensive animals. Previous studies indicate that factors other than blood pressure can influence cardiac hypertrophy. In the present experiments, we evaluated the effects of different sodium diets in the two-kidney, one clip hypertension model in the rat. After the renal artery had been cupped, the rats received a normal sodium (177 meq/kg), high sodium (517 meq/kg), and low sodium (7 meq/kg) diet during 4 weeks. The final blood pressure was almost the same in the three groups (normal sodium 170 ±12 mm Hg; low sodium 168 ±4 mm Hg; and high sodium 162 ±7 mm Hg). Sodium restriction significantly reduced the development of cardiac hypertrophy as compared with rats on normal or high sodium diets. Thus, ventricular weight and ventricular weight/body weight ratio were significantly higher in rats subjected to a normal or high sodium diet (p<0.01). The hypertrophied hearts of rats on normal and high sodium diets showed a larger increase in the number of cardiac ^-adrenergk receptors than those observed in hearts from low sodium diet, clipped rats. These results show that sodium modulates the development of cardiac hypertrophy in two-kidney, one clip hypertensive rats. Similarly, the cardiac /3-adrenergic receptors appear to be influenced by dietary sodium intake. A possible role of the sympathetic nervous system is suggested. (Hypertension 1990;15(suppl I):I-157-I-160)

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1. Rats on normal sodium diet (group 1) and on chronically maintained low sodium diet (group 2) were studied during a control period, after clipping the renal artery (two-kidney, one-clip hypertension) and after nephrectomy (one-kidney, one-clip hypertension). 2. The low sodium diet neither prevented the development nor changed the severity of two-kidney, one-clip hypertension, and the latter was not accompanied by an increase in plasma renin activity. 3. After nephrectomy arterial pressure further increased and plasma renin activity decreased in group 1, and both remained unchanged in group 2. 4. Blood volume was the same in both groups 10 days before and 10 days after nephrectomy. 5. Sodium does not seem to be 'necessary' in the two-kidney, one-clip hypertension although it may play an enhancing role in the one-kidney model.

We hypothesized that in cardiac muscles, angiotensin II partially inhibits the contractile response to beta-agonists. We studied the contractile response of isolated rat left ventricular papillary muscles to isoproterenol and the effect of angiotensin II on this response. We also investigated whether the effect of angiotensin II is mediated by bradykinin, prostaglandins, nitric oxide, and/or cGMP. Contractility of isolated papillary muscles was recorded with a force transducer, and rest tension, maximal developed tension (DT), maximal rate of rise in developed tension [T(+)], and maximal velocity of relaxation [T(-)] were measured (1) under basal conditions, (2) after pretreatment with various drugs, and (3) after cumulative doses of isoproterenol. Pretreatment groups included (1) vehicle (controls); (2) angiotensin II; (3) angiotensin II and N(omega)-nitro-L-arginine, an inhibitor of nitric oxide release; (4) L-arginine, the substrate for nitric oxide synthase; (5) L-arginine and N(omega)-nitro-L-arginine; (6) 8-bromo-cGMP, analogous to the second messenger of nitric oxide; (7) angiotensin II and icatibant (Hoe 140), a bradykinin B2 antagonist; and (8) angiotensin II and indomethacin, a cyclooxygenase inhibitor. There were no differences in contractile parameters before and after any of the pretreatments. Isoproterenol increased DT, T(+), and T(-), and these effects were attenuated by angiotensin II, L-arginine, and 8-bromo-cGMP. The effects of angiotensin II and L-arginine were blocked by inhibition of nitric oxide release with N(omega)-nitro-L-arginine. Neither the bradykinin B2 antagonist nor the cyclooxygenase inhibitor altered the effects of angiotensin II. We concluded that angiotensin II partially inhibits the contractile response of cardiac papillary muscles to isoproterenol This effect is likely mediated by nitric oxide release, perhaps acting via cGMP. Kinins and prostaglandins do not appear to participate in the inhibitory effect of angiotensin II. Attenuation of the contractile effect of isoproterenol by angiotensin II may help explain why cardiac function improves in heart failure after blockade of the renin-angiotensin system.