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(Hypertension. 2002;39:825.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Serotonin-Induced Contraction in Mesenteric Resistance Arteries

Signaling and Changes in Deoxycorticosterone Acetate–Salt Hypertension

Stephanie W. Watts

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

Correspondence to Stephanie W. Watts, PhD, B445 Life Sciences Building, Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI 48824-1317. E-mail wattss{at}msu.edu

Large arteries from hypertensive subjects are hyperresponsiveness to 5-hydroxytryptamine (5-HT). We tested the hypothesis that small arteries (225 µ ID) have a profile similar to conduit arteries, including signal transduction mechanisms and the 5-HT receptor subtype(s) mediating arterial contraction in normal and high blood pressure. Aorta and mesenteric arteries from Sprague-Dawley (232±6 µ ID), sham (229±7 µ ID; systolic blood pressure, 120±2 mm Hg), or deoxycorticosterone acetate (DOCA)–salt rats (255±11 µ ID, 192±8 mm Hg) were mounted in a wire-based myograph. In resistance arteries from Sprague-Dawley rats, the 5-HT_2A receptor mediated contraction; agonists of the 5-HT_1B, 5-HT_1D, 5-HT_1F, and 5-HT_2B receptor were inactive. The tyrosine kinase inhibitor genistein (5 µmol/L, 4.8-fold rightward shift), PD 098,059 (10 µmol/L, 3.2-fold shift), phospholipase C inhibitor NCDC (100 µmol/L), and nifedipine (50 nmol/L) reduced maximum 5-HT–induced contraction in small arteries (4.5% and 53% control, respectively). As in aorta, 5-HT had a decrease in threshold (100-fold lower), increase in potency (11.6-fold leftward shift), and increase in efficacy (140% sham response) in small arteries from DOCA-salt rats compared with sham. Unlike in aorta, 5-HT–induced contraction in DOCA-salt small arteries was shifted competitively by the 5-HT_2A receptor antagonist ketanserin (-log K_B [mol/L] for both sham and DOCA-salt, 9.25±0.1), and contraction to the 5-HT_2B agonist BW723C86 was not observed. Thus, the 5-HT_2A receptor remains the contractile receptor in hypertension in small arteries. Although similarities were observed for large and small arteries, differences under the condition of DOCA-salt hypertension exist that may determine serotonergic compounds effective in lowering blood pressure.

Key Words: 5-hydroxytryptamine • resistance • deoxycorticosterone

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