Premium
Relaxation and decrease in [Ca 2+ ] i by hydrochlorothiazide in guinea‐pig isolated mesenteric arteries
Author(s) -
Pickkers Peter,
Hughes Alun D.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb17195.x
Subject(s) - hydrochlorothiazide , chemistry , mesenteric arteries , medicine , endocrinology , hyperpolarization (physics) , biophysics , biology , artery , blood pressure , organic chemistry , nuclear magnetic resonance spectroscopy
1 We examined the effect of the thiazide diuretic, hydrochlorothiazide, on intracellular calcium concentration ([Ca 2+ ] i ) and tone in guinea‐pig mesentery arteries. Vessels were mounted on a microvascular myograph and loaded with the Ca 2+ ‐sensitive fluorescent dye, Fura‐2. 2 Hydrochlorothiazide caused relaxation of noradrenaline‐precontracted arteries associated with a fall in [Ca 2+ ] i . Preincubation of arteries with hydrochlorothiazide inhibited both contraction and rise in [Ca 2+ ] i in response to noradrenaline. Hydrochlorothiazide did not affect tone and [Ca 2+ ] i when this was elevated by a combination of depolarizing potassium solution and noradrenaline. 3 Hydrochlorothiazide‐induced vasorelaxation and decrease of [Ca 2+ ] i was abolished by charybdotoxin, a blocker of large conductance Ca 2+ ‐activated K channels. 4 The rise in [Ca 2+ ] i elicited by caffeine in Ca 2+ ‐free physiological salt solution, and presumably reflecting Ca 2+ release from intracellular stores, was not altered by preincubation with hydrochlorothiazide. 5 Under depolarizing conditions hydrochlorothiazide did not alter the relationship between the extracellular concentration of Ca 2+ and [Ca 2+ ] i ; however, hydrochlorothiazide caused a small reduction in the contraction produced for a given rise in [Ca 2+ ] i suggesting hydrochlorothiazide may cause a slight desensitization of the contractile machinery. 6 These findings suggest that hydrochlorothiazide opens Ca 2+ ‐activated K channels leading to hyperpolarization and consequent closing of voltage‐operated calcium channels. The result of this is an impaired influx of extracellular Ca 2+ , a decrease in [Ca 2+ ] i and vasorelaxation.