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Diversity in supercoupling of β 2 ‐adrenergic receptors in orthostatic hypotension
Author(s) -
Mares Adolph,
Davies Albert O,
Taylor Addison A
Publication year - 1990
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1990.42
Subject(s) - orthostatic vital signs , chronotropic , medicine , supine position , heart rate , valsalva maneuver , endocrinology , adrenergic , blood pressure , adrenergic receptor , adrenergic antagonist , mean arterial pressure , receptor
Orthostatic hypotension is a clinical condition that frequently involves abnormal adrenergic control of cardiovascular function. Adrenergic function was studied in six patients with symptomatic orthostatic hypotension and in 11 age‐matched healthy subjects. The patients demonstrated higher supine mean arterial pressures (MAP; 103 ± 8 versus 86 ± 4 mm Hg) and orthostatic hypotension (ΔMAP −70 ± 5 versus +15 ± 2 mm Hg, p < 0.001) compared with normal subjects. The ΔMAP in phase II of the Valsalva maneuver was significantly greater (− 31 ± 4 versus −7 ± 4 mm Hg, p < 0.002) and phase IV heart rate response was blunted (−5 ± 3 versus −30 ± 8 beats/min, p < 0.02) in these patients. More isoproterenol was required to increase heart rate by 25 beats per minute in patients with hypotension (810 ± 670 versus 3.1 ± 1.3 μg, p < 0.05), indicating marked chronotropic hyposensitivity. Leukocyte β 2 ‐adrenergic receptor densities were similar in patients and controls. β 2 ‐Adrenergic receptor coupling, however, was elevated in patients with hypotension when compared with control subjects (ratio of the low‐affinity and high‐affinity dissociation constants [K L /K H ] 140 ± 7.4 versus 66 ± 4.3, p < 0.001). There were negative correlations between the K L /K H value and the dose of isoproterenol required to decrease MAP by 20 torr ( p < 0.02) and between the K L /K H value and the product of the hormone receptor and MAP ( p < 0.01). However, the patients could be subdivided into a group who could mount a nearly normal hormone receptor times MAP response on standing (group 1A), and a group who could not (group 1B). The group 1A patients had elevated plasma norepinephrine responses associated with milder β 2 ‐adrenergic receptor supercoupling, whereas group 1B patients had essentially no orthostatic plasma norepinephrine response and had much higher K L /K H values. Thus, though a state of biochemical supersensitivity existed in both patient subgroups, diminished catecholamine exposure was associated, as expected, with β 2 ‐adrenergic hypersensitivity in group 1B, whereas there was no diminution of catecholamine exposure in the β 2 ‐adrenergic hypersensitity observed in group 1A patients. Clinical Pharmacology and Therapeutics (1990) 47, 371–381; doi: 10.1038/clpt.1990.42