Preserved cardiac beta-adrenergic sensitivity in early renovascular hypertension.

Abstract

SUMMARY To determine the mechanism of blunted sympathetic reflex responses in early renovascular hypertension, we measured inotropic and chronotropic responses of the heart to /3-adrenergic stimulation in vivo and myocardial /3-adrenergic receptor number and adenylate cyclase activity in 10 dogs during an early stage of one-kidney renal hypertension. Mean aortic pressure was higher hi the hypertensive dogs (152 ± 4 mm Hg) than in eight sham-operated dogs (122 ± 1 mm Hg; p < 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/mm) 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 /3-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 /3-adrenergic stimulation nor /3-adrenergic desensitization of the myocardium, as assessed by /3-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 /3-adrenergic receptor-adenylate cyclase complex. Supported in part by Public Health Service Grants HL-07220, HL-30194, and AG-03234 and by a grant from the Genesee Valley Chapter of the American Heart Association, New York Affiliate.Presented in part at the 34th annual meeting of the American College of Cardiology at Anaheim, California, March 12, 1985.Address for reprints: Chang-seng Liang, M.D., Ph.D., Cardiology Research Laboratories, Box679, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642.Received August 11, 1986; accepted October 15, 1986. in animals with established renovascular hypertension 2 ' 3 and correlated with reduced myocardial /3-adrenergic receptor number. 43 However, whether similar changes occur during early hypertension is not known. The purpose of the present study was to determine whether myocardial /3-adrenergic desensitization contributed to the blunted reflex responses observed in early renal hypertension. Experiments were performed in two groups of chronically instrumented dogs, soon after the establishment of one-kidney renal hypertension in one group and sham operations in the other normotensive control group. We measured responses of heart rate and rate of left ventricular pressure rise (left ventricular dP/dt) to isoproterenol and to pinacidil, a d...