beta-Receptors and contractile reserve in left ventricular hypertrophy.
The inotropic responsiveness to adrenergic stimulation is diminished in hypertension associated with left ventricular hypertrophy (LVH). This was shown in hypertrophied hearts from renal hypertensive rats (RHR) (two-kidney, one clip hypertension, Goldblatt) 6 weeks after renal artery clipping when compared to age-matched normotensive sham-operated controls (NR). The isoproterenol-stimulated inotropic responses (delta peak dP/dt) of isolated hearts perfused at constant pressure were significantly lower in RHR than in NR (p less than 0.001 by analysis of variance and covariance, including repeated measures). This reduction in ventricular responsiveness of isolated hearts from RHR did not extend to other inotropic agents such as calcium ions and the cardiotonic cardiac glycoside scillaren. Assay of beta-adrenergic receptors by binding to (-) [3H] dihydroalprenolol showed that left ventricular beta-receptor numbers (fmol per mg membrane protein) were significantly reduced in RHR compared to NR (28.2 +/- 1.1 vs 36 +/- 2.6, p less than 0.01) with no significant change in affinity (Kd,nM) (1.9 +/- 0.27 vs 2.26 +/- 0.34,NS). The results of this study suggest that LVH in renovascular hypertension is associated with impairment in inotropic responsiveness to beta-receptor stimulation parallel with and, in part, related to, a reduction in ventricular beta-receptor concentrations. Such blunting of inotropic responsiveness to beta-adrenergic stimulation may be one of the mechanisms in the progression from LVH to heart failure in hypertensive disease.
D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006977:Hypertension, Renal / Q000150:complications*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013268:Stimulation, Chemical
D002301:Cardiac Glycosides; D002316:Cardiotonic Agents; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C026482:scillaren; D007545:Isoproterenol; D002122:Calcium Chloride