Preserved cardiac beta-adrenergic sensitivity in early renovascular hypertension.

To determine the mechanism of blunted sympathetic reflex responses in early renovascular hypertension, we measured inotropic and chronotropic responses of the heart to beta-adrenergic stimulation in vivo and myocardial beta-adrenergic receptor number and adenylate cyclase activity in 10 dogs during an early stage of one-kidney renal hypertension. Mean aortic pressure was higher in the hypertensive dogs (152 +/- 4 mm Hg) than in eight sham-operated dogs (122 +/- 1 mm Hg; p less than 0.001), but heart rate, cardiac output, and left atrial pressure did not differ between the two groups. Blood pressure reduction with a direct-acting vasodilator, pinacidil, resulted in marked increases in heart rate (+97 +/- 12 beats/min) and rate of change of left ventricular pressure (dP/dt; +1447 +/- 367 mm Hg/sec) in normotensive dogs but only blunted heart rate (+54 +/- 12 beats/min) and minimal left ventricular dP/dt (+376 +/- 264 mm Hg/sec) responses in hypertensive dogs. In contrast, intravenously administered isoproterenol produced similar increases in heart rate and left ventricular dP/dt in the two groups. These two groups also did not differ in either left ventricular beta-adrenergic receptor number and affinity or basal, isoproterenol-stimulated, and fluoride-stimulated adenylate cyclase activity. Thus, despite blunted reflex responses to blood pressure reduction, hypertensive dogs showed neither reduction in chronotropic and inotropic responses to direct beta-adrenergic stimulation nor beta-adrenergic desensitization of the myocardium, as assessed by beta-adrenergic receptor number and adenylate cyclase activity. Blunted reflex responses in this model of early hypertension must be due to factors operating at some locus other than the beta-adrenergic receptor-adenylate cyclase complex.