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

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.