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.