Inotropic Responsiveness in Hypertensive Left Ventricular Hypertrophy: Impaired Inotropic Response to Glucagon and Vasoactive Intestinal Peptide in Renal Hypertensive Rats

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Abstract
Previous studies have shown that left ventricular (LV) hypertrophy in renal hypertensive rats (RHR) is associated with reduced responsiveness to .beta.-adrenergic stimulation (isoproterenol) but not to calcium or cardiac glycosides. To determine whether this impairment is restricted to .beta.-receptor agonists or extended to include other stimulants of the adenylate cyclase system, inotropic responses to glucagon and to vasoactive intestinal peptide (VIP) were determined in isolated paced hearts (Langendorff preparation) from RHR and strictly matched sham-operated controls. The response (.DELTA. peak LV + dP/dt) to both agonists was significantly reduced in RHR, whether expressed in absolute value or in percent of baseline. It averaged 59.3 .+-. 19.3 (SE) mm Hg .cntdot. s-1 in RHR at the highest dose of VIP (15 .mu.g) and a perfusion pressure (PP) of 50 mm Hg as compared with 255 .+-. 68.4 in controls (p < 0.01). The responses to glucagon were determined at two levels of perfusion pressure.sbd.50 and 80 mm Hg.sbd.to determine the influence, if any, of possible alterations in myocardial perfusion on differences between the normal and hypertrophied hearts. At both PP levels the LV + dP/dt response was significantly lower in RHR.sbd.+374 .+-. 103 vs. +1,026 .+-. 166 mm Hg .cntdot. s-1 (p < 0.005) for +120 .+-. 5 vs. +143 .+-. 7% of baseline value (p < 0.02) for PP of 50 mm Hg; and 392 .+-. 154 vs. +1,732 .+-. 251 mm Hg .cntdot. s-1 (p < 0.01) or +112 .+-. 4 vs. +160 .+-. 2% (p < 0.001) for PP of 800 mm Hg. The same significant (p < 0.05 at maximum response to glucagon) reduction in response was obtained in hearts from RHR when compared at equal levels of myocardial perfusion rate with normal controls. Since both VIP and glucagon act each through its specific receptor, the results indicate that the impairment in inotropic responsiveness associated with LV hypertrophy in RHR is not exclusively dependent on a .beta.-receptor abnormality but extends to different agonists of the adenylate cyclase system. Moreover, the impaired response was not dependent on differences in myocardial flow rate between hypertrophied and normal ventricles.