Article date: February 1995
By: Peter Pickkers, Alun D. Hughes, in Volume 114, Issue 3, pages 703-707
We examined the effect of the thiazide diuretic, hydrochlorothiazide, on intracellular calcium concentration ([Ca2+]i) and tone in guinea‐pig mesentery arteries. Vessels were mounted on a microvascular myograph and loaded with the Ca2+‐sensitive fluorescent dye, Fura‐2.
Hydrochlorothiazide caused relaxation of noradrenaline‐precontracted arteries associated with a fall in [Ca2+]i. Preincubation of arteries with hydrochlorothiazide inhibited both contraction and rise in [Ca2+]i in response to noradrenaline. Hydrochlorothiazide did not affect tone and [Ca2+]i when this was elevated by a combination of depolarizing potassium solution and noradrenaline.
Hydrochlorothiazide‐induced vasorelaxation and decrease of [Ca2+]i was abolished by charybdotoxin, a blocker of large conductance Ca2+‐activated K channels.
The rise in [Ca2+]i elicited by caffeine in Ca2+‐free physiological salt solution, and presumably reflecting Ca2+ release from intracellular stores, was not altered by preincubation with hydrochlorothiazide.
Under depolarizing conditions hydrochlorothiazide did not alter the relationship between the extracellular concentration of Ca2+ and [Ca2+]i; however, hydrochlorothiazide caused a small reduction in the contraction produced for a given rise in [Ca2+]i suggesting hydrochlorothiazide may cause a slight desensitization of the contractile machinery.
These findings suggest that hydrochlorothiazide opens Ca2+‐activated K channels leading to hyperpolarization and consequent closing of voltage‐operated calcium channels. The result of this is an impaired influx of extracellular Ca2+, a decrease in [Ca2+]i and vasorelaxation.
We examined the effect of the thiazide diuretic, hydrochlorothiazide, on intracellular calcium concentration ([Ca2+]i) and tone in guinea‐pig mesentery arteries. Vessels were mounted on a microvascular myograph and loaded with the Ca2+‐sensitive fluorescent dye, Fura‐2.
Hydrochlorothiazide caused relaxation of noradrenaline‐precontracted arteries associated with a fall in [Ca2+]i. Preincubation of arteries with hydrochlorothiazide inhibited both contraction and rise in [Ca2+]i in response to noradrenaline. Hydrochlorothiazide did not affect tone and [Ca2+]i when this was elevated by a combination of depolarizing potassium solution and noradrenaline.
Hydrochlorothiazide‐induced vasorelaxation and decrease of [Ca2+]i was abolished by charybdotoxin, a blocker of large conductance Ca2+‐activated K channels.
The rise in [Ca2+]i elicited by caffeine in Ca2+‐free physiological salt solution, and presumably reflecting Ca2+ release from intracellular stores, was not altered by preincubation with hydrochlorothiazide.
Under depolarizing conditions hydrochlorothiazide did not alter the relationship between the extracellular concentration of Ca2+ and [Ca2+]i; however, hydrochlorothiazide caused a small reduction in the contraction produced for a given rise in [Ca2+]i suggesting hydrochlorothiazide may cause a slight desensitization of the contractile machinery.
These findings suggest that hydrochlorothiazide opens Ca2+‐activated K channels leading to hyperpolarization and consequent closing of voltage‐operated calcium channels. The result of this is an impaired influx of extracellular Ca2+, a decrease in [Ca2+]i and vasorelaxation.
DOI: 10.1111/j.1476-5381.1995.tb17195.x
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