Hemodynamics of the Spontaneously Hypertensive Rat: Effects of Isoproterenol 1

Increased sympathetic neural activity has been implicated in the pathogenesis and maintenance of elevated arterial pressure in several forms of hypertension. Although increased adrenergic participation may alter cardiovascular performance by modifying both vascular smooth and cardiac muscle function, the effect upon the latter has received little attention. Fujiwara, Kuchii, and Shibata have recently reported that atria isolated from spontaneously hypertensive rats (SHR) exhibited lesser increments of cardiac responses from isoproterenol stimulation than normotensive rat atria (NR) (1). In our previous studies, the intact SHR myocardium failed to demonstrate the increases in heart rate and cardiac output which were observed in sex- and age-matched NR during infusions of small doses of exogenously administered norepinephrine (5). These differences of cardiac responses to norepinephrine could indicate possible quantitative or qualitative alterations in the cardiac administered sympathetic neurotransmitter, intrinsic changes in the myocardial contractile machinery, or possible differences in tonic autonomic influences on myocardial function. The present study was undertaken to examine further the responses of intact NR and SHR myocardia to betaadrenergic stimulation with the specific agonist isoproterenol.

Methods. Studies were performed on the 21st and 22nd filial generation of spontaneously hypertensive rats (3) and on normotensive Wistar rats (West Jersey Biological Supply) ranging from 22 to 27 weeks of age. Commercially obtained normotensive Wistar rats (from the original Wistar strain) were used since Wistar-Kyoto (WKY) rats were not available at the time this study was initiated. In previous studies we have compared the hemodynamic and myocardial functions of these two groups of rats over a wide range (6) and following acute elevation of arterial pressure (5). It was therefore necessary to follow up the mechanisms for these observed differences, and present studies