Serotonin-Induced Contraction in Mesenteric Resistance Arteries: Signaling and Changes in Deoxycorticosterone Acetate–Salt Hypertension

Abstract

Large arteries from hypertensive subjects are hyperresponsiveness to 5-hydroxytryptamine (5-HT). We tested the hypothesis that small arteries (225 &mgr; 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 &mgr; ID), sham (229±7 &mgr; ID; systolic blood pressure, 120±2 mm Hg), or deoxycorticosterone acetate (DOCA)–salt rats (255±11 &mgr; ID, 192±8 mm Hg) were mounted in a wire-based myograph. In resistance arteries from Sprague-Dawley rats, the 5-HT2A receptor mediated contraction; agonists of the 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT2B receptor were inactive. The tyrosine kinase inhibitor genistein (5 &mgr;mol/L, 4.8-fold rightward shift), PD 098,059 (10 &mgr;mol/L, 3.2-fold shift), phospholipase C inhibitor NCDC (100 &mgr;mol/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-HT2A receptor antagonist ketanserin (−log KB [mol/L] for both sham and DOCA-salt, 9.25±0.1), and contraction to the 5-HT2B agonist BW723C86 was not observed. Thus, the 5-HT2A 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.