Reversal of changes in myocardial beta-receptors and inotropic responsiveness with regression of cardiac hypertrophy in renal hypertensive rats (RHR).
Our previous studies, in vivo and in vitro, have shown reduced inotropic responsiveness to isoproterenol of hypertrophied hearts in renovascular hypertensive rats. In the present study, we have investigated, in the same model, the effects of treatment either by nephrectomy or captopril on the inotropic responsiveness to isoproterenol and on the number and affinity of ventricular beta-receptors. Isoproterenol infusion of isolated hearts from renovascular hypertensive rats 12-18 weeks post-clipping produced lower inotropic responses (delta peak dP/dt) than age-matched sham-operated normotensive rats (P less than 0.001). Quantitative assessment of beta-adrenergic receptors in the same hearts showed a significant decrease in renovascular hypertensive rats ventricular receptor numbers, whether calculated per milligram membrane protein (22.3 +/- 2.66 fmol/mg vs. 37.9 +/- 4.34, P less than 0.005) or per gram wet ventricular weight (1.43 +/- 0.14 pmol/g vs. 2.2 +/- 0.21, P less than 0.005), with no significant change in Kd. Control of hypertension by either nephrectomy or captopril led to regression of hypertrophy 6 weeks after stabilization of blood pressure (12-18 weeks post-clipping) and returned both the ventricular receptor density and inotropic responsiveness toward normal. The improvement in inotropic responsiveness to isoproterenol in regressed hearts correlated with both the reduction in ventricular weight and the decrease of blood pressure. Regression of hypertrophy did not alter the relationship between inotropic response, receptor density, and ventricular weight. These results indicate that the increase in cardiac mass associated with renovascular hypertension may interfere with adrenergic support to the heart, and that proper control of hypertension and regression of hypertrophy could reverse that impairment and restore its responsiveness to adrenergic stimulation.
D000818:Animals; D002216:Captopril / Q000627:therapeutic use; D006332:Cardiomegaly / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D006977:Hypertension, Renal / Q000150:complications* / Q000601:surgery; D007545:Isoproterenol / Q000627:therapeutic use; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009392:Nephrectomy; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D002216:Captopril; D007545:Isoproterenol