Impaired cardiac contractile response to isoproterenol in the spontaneously hypertensive rat.
To test the ability of the hypertrophied ventricle to increase its contractility in response to sympathetic stimulation, we compared the chronotropic, inotropic, and relaxation responses to graded in fusions 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 micrograms/kg/min) for a significant chronotropic response, and their maximal response of heart rate was smaller than in WKY (delta HR = +12.5 +/- 5.4 vs +22.8 +/- 10.7 beats/min, p less than 0.01). Contractility indices did not increase in the SHR after isoproterenol infusion: (delta dP/dt +2224.3 +/- 1304.7 mm Hg/sec; delta dP/dt/P = +5.1 +/- 9.3 sec-1, p greater than 0.05) in sharp contrast with the marked increases observed in WKY (delta dP/dt = +4682.1 +/- 435.0 mm Hg/sec, p less than 0.01; delta dP/dt/P +78.6 +/- 8.0 sec-1, p less than 0.001). Left ventricular relaxation rate was marked diminished by isoproterenol in SHR (delta neg dP/dt = -2598.6 +/- 855.0 mm Hg/sec) whereas it was not altered significantly in normotensive 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.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D011674:Pulse / Q000187:drug effects; D051381:Rats; D013997:Time Factors
D007545:Isoproterenol