TY - JOUR
T1 - Myocardial beta-adrenergic receptors in the stroke-prone spontaneously hypertensive rat
AU - Mukherjee, A.
AU - Graham, R. M.
AU - Sagalowsky, Arthur I
AU - Pettinger, W.
AU - McCoy, K. E.
N1 - Funding Information:
We are most grateful to Dr W. Lovenberg (NIH, Bethesda, Md.) for supply of the sp-SHR, MS J. Zimmer and Mr W. H. Stephenson for expert technical assistance and MS C. Johns for secretarial assistance. Dr Robert M. Graham is a Pharmaceutical Manufacturer’s Association Career Development Awardee and Dr Arthur I. Sagalowsky is an American Urological Association Scholar. This work was supported by the NIH Ischemic Heart SCOR Grant HL-17669, the Harry S. Moss Heart Fund, NIH grant l-ROl-HL24480-01 and a grant from the American Heart Association, Texas affiliate.
PY - 1980
Y1 - 1980
N2 - In view of the severity of the hypertension in the stroke-prone spontaneously hypertensive rats (sp-SHR), myocardial beta-adrenergic receptors were investigated by the binding of (−)[3H]-dihydroalprenolol (DHA) to membranes from sp-SHR (9-week-old males, Okamoto-Aoki strain) and age-matched and sex-matched normotensive Wistar-Kyoto rats. Scatchard analysis showed no significant differences in binding parameters between sp-SHR and normal rats. Myocardial membranes from sp-SHR bound 31.8 ± 2.3 fmol DNA per mg protein with a dissociation constant of 3.8 ± 0.9 nm, whereas membranes from normal rats bound 33.4 ± 2.9 fmol DHA per mg protein with a dissociation constant of 3.9 ± 1.0 nm. However, mean arterial pressure and heart rate determined directly via aortic cannulae, while the rats were conscious and unrestrained, were significantly higher in sp-SHR. Plasma norepinephrine concentration was also significantly higher in sp-SHR. The finding that cardiac beta-adrenergic receptors are unchanged, despite evidence of increased sympathetic nerve activity, suggests that in the sp-SHR there may be a failure of catecholamine-induced “down regulation” of beta-adrenergic receptors. This defect could contribute to the increased cardiac drive in these animals and may thus explain the severity of the hypertension in this strain of spontaneously hypertensive rats.
AB - In view of the severity of the hypertension in the stroke-prone spontaneously hypertensive rats (sp-SHR), myocardial beta-adrenergic receptors were investigated by the binding of (−)[3H]-dihydroalprenolol (DHA) to membranes from sp-SHR (9-week-old males, Okamoto-Aoki strain) and age-matched and sex-matched normotensive Wistar-Kyoto rats. Scatchard analysis showed no significant differences in binding parameters between sp-SHR and normal rats. Myocardial membranes from sp-SHR bound 31.8 ± 2.3 fmol DNA per mg protein with a dissociation constant of 3.8 ± 0.9 nm, whereas membranes from normal rats bound 33.4 ± 2.9 fmol DHA per mg protein with a dissociation constant of 3.9 ± 1.0 nm. However, mean arterial pressure and heart rate determined directly via aortic cannulae, while the rats were conscious and unrestrained, were significantly higher in sp-SHR. Plasma norepinephrine concentration was also significantly higher in sp-SHR. The finding that cardiac beta-adrenergic receptors are unchanged, despite evidence of increased sympathetic nerve activity, suggests that in the sp-SHR there may be a failure of catecholamine-induced “down regulation” of beta-adrenergic receptors. This defect could contribute to the increased cardiac drive in these animals and may thus explain the severity of the hypertension in this strain of spontaneously hypertensive rats.
KW - Beta-receptors
KW - Myocardium
KW - Spontaneously hypertensive
KW - [H]dihydroalprenolol
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U2 - 10.1016/0022-2828(80)90070-X
DO - 10.1016/0022-2828(80)90070-X
M3 - Article
C2 - 6255168
AN - SCOPUS:0019135930
SN - 0022-2828
VL - 12
SP - 1263
EP - 1272
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 11
ER -