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Am J Physiol Heart Circ Physiol 290: H1251-H1258, 2006. First published November 4, 2005; doi:10.1152/ajpheart.00203.2005
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In vivo evidence for endothelin-1-mediated attenuation of {alpha}1-adrenergic stimulation

Gerard D’Angelo,1,2 Jennifer S. Pollock,1,2,3 and David M. Pollock1,2,3,4

1Vascular Biology Center, Departments of 2Physiology, 3Pharmacology, and 4Surgery, Medical College of Georgia, Augusta, Georgia

Submitted 2 March 2005 ; accepted in final form 31 October 2005

Experiments were designed to determine the influence of endothelin A (ETA) receptors on the pressor response to acute environmental stress in Dahl salt-resistant (DR) and Dahl-sensitive (DS) rats. Mean arterial pressure (MAP) was chronically monitored by telemetry before and after treatment with the selective ETA receptor antagonist ABT-627. Rats were restrained and subjected to pulsatile air jet stress (3 min). In untreated animals, the total pressor response (area under the curve) to acute stress was not different between DR vs. DS rats (8.1 ± 1.7 vs. 15.6 ± 2.6 mmHg x 3 min, P = 0.10). Conversely, treatment with ABT-627 potentiated the total pressor response only in DR rats (36.3 ± 6.2 vs. 22.6 ± 5.9 mmHg x 3 min, DR vs. DS, P < 0.05). Treatment with ABT-627 allowed greater responses in anesthetized DR rats to exogenous phenylephrine (1–4 µg/kg) during ganglionic blockade (P < 0.05) and produced a significant increase in plasma norepinephrine at baseline and during stress in conscious DR rats compared with untreated animals (P < 0.05). ETA receptor blockade had no effect on these responses in DS rats. Our results suggest that endothelin-1 can inhibit {alpha}-adrenergic-mediated effects in DR, but not DS rats, consistent with the hypothesis that ETA receptor activation functions to reduce sympathetic nerve activity and responses in vascular smooth muscle to sympathetic stimulation.

vascular smooth muscle; salt-sensitive hypertension; sympathetic nervous system


Address for reprint requests and other correspondence: G. D’Angelo, Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912-2500 (e-mail: gdangelo{at}mail.mcg.edu)




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S. B. Bender and R. E. Klabunde
Altered role of smooth muscle endothelin receptors in coronary endothelin-1 and {alpha}1-adrenoceptor-mediated vasoconstriction in Type 2 diabetes
Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2281 - H2288.
[Abstract] [Full Text] [PDF]


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