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(Hypertension. 2001;38:891.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Enhanced Contraction to 5-Hydroxytryptamine Is Not Due to "Unmasking" of 5-Hydroxytryptamine_1B Receptors in the Mesenteric Artery of the Deoxycorticosterone Acetate–Salt Rat

Amy K.L. Banes; Stephanie W. Watts

From the Department of Pharmacology and Toxicology, Michigan State University, East Lansing.

Reprint requests to Amy Banes, Department of Pharmacology and Toxicology, Michigan State University, B445 Life Sciences Bldg, East Lansing, MI 48824. E-mail banesamy{at}msu.edu

Abstract—— 5-Hydroxytryptamine_1B (5-HT_1B) receptors have been implicated in mediating arterial contraction to 5-HT. Additionally, the 5-HT_1B receptor has been reported to be "unmasked" by depolarizing stimuli. We hypothesized that 5-HT_1B receptors in arteries from hypertensive animals, arteries reported to have a depolarized resting membrane potential in smooth muscle cells, are unmasked and participate in the supersensitivity observed to 5-HT in hypertension. We used the isolated tissue bath apparatus and examined the response of superior mesenteric arteries from normotensive sham and hypertensive deoxycorticosterone acetate (DOCA)–salt rats. The 5-HT_1B agonists CP93129 and sumatriptan (10^-9 to 10^-5 mol/L) caused a maximal contraction (50±12% of phenylephrine [10^-5 mol/L] contraction) in arteries from DOCA-salt rats; no contraction was observed in arteries from normotensive rats. The 5-HT_1B receptor antagonist GR55562 (100 nmol/L) inhibited both the 5-HT– (4-fold rightward shift) and CP93129-induced (11-fold rightward shift) contractions in mesenteric arteries from hypertensive DOCA-salt rats. In other experiments, arteries from normotensive rats were incubated with 15 mmol/L KCl, as a depolarizing stimulus, and then exposed to 5-HT and CP93129. In the presence of KCl, a small leftward shift to 5-HT was observed. However, the presence of a depolarizing stimulus was unable to produce changes in the 5-HT maximal response to resemble that of arteries from DOCA-salt rats, nor was contraction to CP93129 observed. These data support the conclusions that 5-HT_1B receptors mediate contraction in mesenteric arteries from hypertensive rats and that this enhanced response to 5-HT is not due to membrane depolarization alone.

Key Words: serotonin • mesenteric arteries • vasoconstriction • deoxycorticosterone

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