iodohydroxybenzylpindolol and Hypertension

The authors studied the number of myocardial beta-adrenergic receptors and the cyclic nucleotide concentration in both male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) at 4 to 5, 10 to 15, 20 to 25 and 35 to 55 weeks of age. A potent beta-adrenergic antagonist, (125I) iodohydroxybenzylpindolol was used to estimate the number and affinity of beta-adrenergic receptors. beta-adrenergic receptors in cardiac membranes from SHR of 4 to 5 weeks and 10 to 15 weeks numbered 63.1 +/- 4.6 and 51.6 +/- 4.6 f mol/mg protein, respectively. These were significantly (p less than 0.02) greater than the number in WKY at 4 to 5 weeks and 10 to 15 weeks (42.2 +/- 5.1 and 31.5 +/- 5.4 f mol/mg protein, respectively). The dissociation constant in the membranes was the same in WKY and SHR, and no significant differences were found in the number of receptors and affinity of SHR and WKY at 20 to 25 weeks or 35 to 55 weeks of age. Also, there was no difference in the concentration of myocardial cyclic nucleotides at the various ages. Since cardiac hypertrophy in SHR had appeared before the onset of hypertension at about 7 weeks, the present results suggest that the SHR heart is hypersensitive to catecholamines and hemodynamically hyperkinetic due to the increased numbers of beta-receptors in the pre- and early stages of hypertension.

Topics: Animals; Blood Pressure; Cyclic AMP; Hypertension; Isoproterenol; Male; Myocardium; Pindolol; Rats; Rats, Inbred Strains; Receptors, Adrenergic, beta; Sodium-Potassium-Exchanging ATPase

It has been suggested that beta-adrenergic responsiveness is reduced in hypertension. To evaluate a possible alteration in human beta-receptors that might account for diminished beta-adrenergic responsiveness, we studied leukocytes from hypertensive and normotensive subjects after an overnight rest supine, and then after being ambulatory, a maneuver that increases plasma catecholamines approximately twofold. In supine samples, beta-receptor affinity for the agonist isoproterenol was significantly reduced in hypertensives and was associated with a reduction in the proportion of beta-receptors binding agonist with a high affinity from 42 +/- 6% in normotensive subjects to 25 +/- 2% in hypertensives (P less than 0.05). Alterations in beta-adrenergic-mediated adenylate cyclase activity parallelled the differences seen in the beta-receptor affinity for agonist. In normotensive subjects, beta-receptor density and the proportion of receptors binding agonist with high affinity were reciprocally correlated with plasma catecholamines. However, in the hypertensive subjects these correlations were not evident. Thus, our data suggest an alteration in leukocyte beta-receptor interactions in hypertensive subjects, and may represent a generalized defect in beta-receptor function in hypertension.

Topics: Adenylyl Cyclases; Adult; Binding, Competitive; Epinephrine; Humans; Hypertension; Isoproterenol; Leukocytes; Norepinephrine; Pindolol; Posture; Receptors, Adrenergic, beta

Topics: Adenylyl Cyclases; Animals; Blood Pressure; Blood Vessels; Desoxycorticosterone; Heart; Hypertension; Kinetics; Male; Mesenteric Arteries; Organ Size; Pindolol; Rats; Receptors, Adrenergic; Receptors, Adrenergic, beta