Increased potency of carbachol in isolated rat left atria after chronic reserpine pretreatment

Abstract

Chronic reserpine pretreatment has been shown to produce postjunctional beta-adrenergic supersensitivity in cardiac tissue. The present investigation was undertaken to determine whether chronic reserpine administration also alters the heart's sensitivity to muscarinic cholinoceptor agonists. The direct and indirect (antiadrenergic) negative inotropic effects of muscarinic agonists were examined in isolated rat left atria at various times after initiation of reserpine pretreatment (1.0 mg.kg-1 x day-1 for 7 days). Supersensitivity to the positive inotropic effects of isoproterenol was demonstrated at 1, 2, and 3 wk after initiation of treatment. Concentration-response curves were then obtained for the muscarinic agonist carbachol and the adenosine A1 receptor agonist (-)-N6-(2-phenylisopropyl)-adenosine (PIA) in reducing the inotropic response to isoproterenol (3.16 microM). The potency of carbachol was increased by approximately 2.0-fold at 1, 2, and 3 wk. Also, sensitivity to the direct negative inotropic effects of carbachol was increased 1.7-fold at 1 wk but not at 2 and 3 wk. At 1 wk, reserpine pretreatment did not alter either the direct or the indirect negative inotropic effects of PIA. These results show that postjunctional beta-adrenergic supersensitivity produced by chronic reserpine pretreatment is accompanied by a reciprocal increase in sensitivity of isolated rat left atria to the negative inotropic effects of muscarinic agonists.

Depressed transient outward potassium current density in catecholamine-depleted rat ventricular myocytes

“…We chose to use reserpine because 1) this substance has no effect on I to even if applied directly to the cell or injected 2 h before the animal is killed and 2) this model of catecholamine depletion is the most thoroughly documented in the literature (20,38). Reserpine treatment is well known to decrease tissue norepinephrine content.…”

“…Chemical denervation was induced by reserpine treatment, which is known to decrease the amount of norepinephrine released into tissues by sympathetic nerve terminals (20,38). We found that the depletion of endogenous norepinephrine by reserpine markedly decreased I to density, whereas I sus was unaffected.…”