Is the Serotonin1b Receptor Involved in Arterial Serotonergic Hypersensitivity in Deoxycorticosterone Acetate-Salt Hypertension?

Abstract

P27 The 5-HT1B receptor has been recently implicated in mediating arterial contraction to serotonin (5-hydroxytryptamine, 5-HT).The 5-HT1B receptor is unmasked/enabled by depolarizing stimuli. It is possible that 5-HT1B receptors in arteries from hypertensive animals, arteries reported to have a depolarized resting potential in smooth muscle cells, are enabled and participate in the supersensitivity observed to 5-HT in hypertension. To test this hypothesis, we utilized an isolated tissue bath apparatus and examined the response of thoracic aorta from normotensive sham rats [systolic blood pressure (SBP) 123 +2 mmHg] and hypertensive deoxycorticosterone acetate (DOCA)-salt rats [SBP 194 + 10 mmHg]. The 5-HT1B agonist RU24969 and the 5-HT1B/1D receptor agonist sumatriptan (10-9 -10-5 M) caused a maximal contraction [50 % + 12 of phenylephrine (10-5 M) contraction] in tissues from DOCA-salt rats; no contraction was observed in normotensive arteries. The 5-HT1B antagonist SB216641 (30 nM) was unable to block the RU24969-induced contraction as well as the 5-HT (10-9 -10-4 M)-induced contraction in aorta from both DOCA-salt and normotensive rats. Tissues from normotensive rats were incubated with 15mM KCl as a depolarizing stimulus, and then curves were performed to 5-HT, RU24969, and sumatriptan. These studies were performed in the presence of ketanserin (10 nM, 5-HT 2A receptor antagonist) to remove the contribution of the 5-HT2A receptor. The 5-HT-induced contraction was not changed in the presence of the KCl stimulus. High concentrations (10-5 M) of RU24969 did result in a 30% + 9 contraction. However, the presence of a depolarizing stimulus was unable to produce a leftward shift of the response to resemble that of aorta from DOCA-salt rats. These data support the conclusions that 5-HT1B receptors do not contribute significantly to the 5-HT-induced contraction in the rat aorta or to the hypersensitivity to 5-HT observed in DOCA-salt hypertension. In addition, these data support the conclusion that the arterial hypersensitivity to 5-HT in hypertension is not due to membrane depolarization alone.