Impaired inotropic responses to alpha-adrenergic stimulation in experimental left ventricular hypertrophy.
We have previously reported that left ventricular hypertrophy in two-kidney, one-clip renal hypertensive rats (2K-1C RHRs) was associated with diminished inotropic responsiveness to isoproterenol and glucagon, suggesting an alteration in the receptor-adenylate cyclase cascade. The present study was performed to investigate the hypothesis that in these same hearts, inotropic responses to alpha-adrenergic stimuli could be enhanced as a compensatory mechanism. alpha-Adrenergic stimulation was achieved by graded phenylephrine infusion (1.02 to 41.2 microM/min) in the presence of propranolol (10(-7) M). The inotropic response was evaluated in the isovolumetric isolated rat heart (Langendorff preparation) paced at 260 beats/min. Results showed a significantly reduced inotropic response to alpha 1-adrenergic stimulation in 2K-1C RHR hearts irrespective of perfusion pressure (50 or 80 mm Hg [PP50 or PP80]) (+427.5 +/- 62.1 vs +1236 +/- 216.4 mm Hg X sec-1 at PP50, p less than .01 and +339 +/- 98.3 vs +1440 +/- 254 mg Hg X sec-1 at PP80, p less than .001) even when comparison was made at equivalent myocardial flow rates (RHR hearts perfused at 80 mm Hg vs control hearts perfused at 50 mm Hg). Quantitative assessment of number of alpha 1-adrenergic receptors (3H-prazosin binding) showed a significant decrease compared with that in age-matched sham-operated normotensive control rats (45 +/- 2.5 vs 64 +/- 1.7 fmol/mg protein, p less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Fouad
F M
FM
Shimamatsu
K
K
Hanna
M M
MM
Khairallah
P A
PA
Tarazi
R C
RC
D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000503:physiopathology; D006977:Hypertension, Renal / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D011433:Propranolol; D007545:Isoproterenol