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.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D006146:Guanidines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D020110:Pinacidil; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D006146:Guanidines; D011943:Receptors, Adrenergic, beta; D014665:Vasodilator Agents; D020110:Pinacidil; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine