Impaired cardiac contractile response to isoproterenol in the spontaneously hypertensive rat

Abstract

To test the ability of the hypertrophied ventricle to increase its contractility in response to sympathetic stimulation, we compared the chronotropic, inotroplc, and relaxation responses to graded infusions of isoproterenol in spontaneously hypertensive rats (SHR) with responses of matched Wistar-Kyoto (WKY) controls. A closed-chested, direct ventricle puncture was used for the study. The SHR required a higher threshold dose (0.04 vs 0.01 μg/kg/min) for a significant chronotropic response, and their maximal response of heart rate was smaller than In WKY (ΔHR = +12.5 ± 5.4 vs +22.8 ± 10.7 beats/min, p < 0.01). Contractility indices did not increase in the SHR after isoproterenol infusion: (ΔdP/dt + 22243 ± 1304.7 mm Hg/sec; ΔdP/dt/P = + 5.1 ± 9.3 saec-1p> 0.05) in sharp contrast with the marked Increases observed in WKY (ΔdP/dt = + 4682.1 ± 435.0 mm Hg/sec, p < 0.01; ΔdP/dt/P + 78.6 ± 8.0 sec-1.p < 0.001). Left ventricular relaxation rate was markedly diminished by isoproterenol in SHR (Δneg dP/dt = -2598.6 ± 855.0 mm Hg/sec) whereas it was not altered significantly in nonnotensive rats. Thus, cardiac contractile and chronotropic responses were markedly diminished in SHR, possibly as a result of diminished beta adrenoreceptor mediation; further, the impairment of the relaxation rate induced by isoproterenol in SHR might also interfere with contractile cardiac performance during stress. © 1981 American Heart Association, Inc.