Alterations of myocardial alpha 1-adrenergic receptors in hypertensive cardiac hypertrophy in the rat
Hanna, M.K.; Khairallah, P.A.
Archives Internationales de Pharmacodynamie et de Therapie 283(1): 80-93
1986
ISSN/ISBN: 0003-9780 PMID: 3026269 Document Number: 271511
The hypertrophied myocardium of 2 kidney-1 clip renal hypertensive rats (2K-1C RHR) displays reduced responsiveness to phenylephrine stimulation. We have studied the effects of hypertrophy on alpha 1-receptor binding properties in three models of hypertension. Specific binding density of an alpha 1-selective antagonist [3H]-prazosin to ventricular membrane of 6 and 10 weeks 2K-1C RHR was significantly decreased (45 +/- 9 fmol/mg protein, n = 14, vs 64 +/- 7.8 fmol/mg protein, n = 20, p less than .001) compared to age matched sham operated control group, but with no change in the total alpha 1-receptor content in the hypertrophied ventricles. The 4 week 1K-1C RHR showed a 29% decrease in alpha 1-adrenergic receptor density with no change in affinity. In contrast, the spontaneously hypertensive rats (SHR) showed an increase in alpha 1-receptors in the prehypertensive stage (4 weeks old) (115.2 +/- 4.9 fmol/mg protein, n = 10, vs 88.7 +/- 12 fmol/mg protein, n = 10, p less than .001) and in the adult stage with established hypertension (15 weeks old) (87.1 +/- 10.5 fmol/mg protein, n = 10, vs 67.3 +/- 9 fmol/mg protein, n = 10, p less than .001) compared to age matched or heart weight matched Wistar Kyoto rats (WKY). Reduced responsiveness to phenylephrine in RHR may be due to reduced density of alpha 1-receptors, but the reason for the increase in alpha 1-receptors in SHR's myocardium remains unclear.