Forearm beta adrenergic receptor-mediated vasodilation is impaired, without alteration of forearm norepinephrine spillover, in borderline hypertension.
Impaired beta adrenoceptor-mediated vasodilation associated with enhanced sympathetic activity has been reported in established hypertension. We examined whether altered beta adrenoceptor-mediated vasodilation occurs early in the disease process, when structural vascular changes are likely to be less marked, by measurement of forearm blood flow by strain gauge plethysmography after the intraarterial administration of increasing doses of a beta receptor agonist, isoproterenol, in eight subjects with borderline hypertension (BHT) and 13 normotensive (NT) controls. To determine the role of sympathetic activation in the regulation of responsiveness, we measured local sympathetic activity in the forearm by a radioisotope dilution technique. Vasodilation in response to isoproterenol, measured either as changes in forearm blood flow or forearm vascular resistance, was impaired in the BHT group so that flow at the highest dose of isoproterenol (400 ng/min) increased less (15.2 +/- 1.5 ml/100 ml per min) than in the NT group (24.4 +/- 2.4 ml/100 ml per minute) (P < 0.001). Although, systemic norepinephrine spillover was significantly greater in BHT, the difference in blood flow response to isoproterenol was not accounted for by increased local sympathetic activity since forearm norepinephrine spillover at baseline (BHT 1.0 +/- 0.4 ng/min vs. NT 0.64 +/- 0.13 ng/min) and after the administration of isoproterenol 60 ng/min (BHT 5.2 +/- 1.4 ng/min vs. NT 6.0 +/- 1.5 ng/min) and 400 ng/min (BHT 13.5 +/- 2.9 ng/min vs. NT 16.5 +/- 2.7 ng/min) did not differ between the two groups. We therefore conclude that vasodilation in response to isoproterenol is impaired in subjects with BHT and that this impairment is not explained by locally increased basal, or stimulated, sympathetic activity.
Stein
C M
CM
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6602, USA.
Nelson
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R
Deegan
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R
He
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Wood
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Wood
A J
AJ
D000328:Adult; D004730:Endothelium, Vascular / Q000502:physiology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D009638:Norepinephrine