Inotropic responsiveness in hypertensive left ventricular hypertrophy: impaired inotropic response to glucagon and vasoactive intestinal peptide in renal hypertensive rats.
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 X s-1 in RHR at the highest dose of VIP (15 micrograms) and a perfusion pressure (PP) of 50 mm Hg as compared with 255 +/- 68.4 in controls (p less than 0.01). The responses to glucagon were determined at two levels of perfusion pressure--50 and 80 mm Hg--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--+ 374 +/- 103 vs. + 1,026 +/- 166 mm Hg X s-1 (p less than 0.005) or + 120 +/- 5 vs. + 143 +/- 7% of baseline value (p less than 0.02) for PP of 50 mm Hg; and 392 +/- 154 vs. + 1,732 +/- 251 mm Hg X s-1 (p less than 0.01) or + 112 +/- 4 vs. + 160 +/- 2% (p less than 0.001) for PP of 80 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)
Fouad
F M
FM
Shimamatsu
K
K
Said
S I
SI
Tarazi
R C
RC
D000818:Animals; D006332:Cardiomegaly / Q000150:complications / Q000503:physiopathology*; D003326:Coronary Circulation; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology*; D006977:Hypertension, Renal / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D014660:Vasoactive Intestinal Peptide; D005934:Glucagon