Arterial function after trichlormethiazide therapy in spontaneously hypertensive rats

M Kahonen, H Makynen, P Arvola, H Wuorela and I Porsti

Medical School, University of Tampere, Finland.

Inasmuch as the long-term influences of diuretic therapy on arterial function remain largely unknown, the effects of trichlormethiazide (8 mg kg-1 day-1) on vascular responses were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. The 14-week treatment attenuated the increase in blood pressure by approximately 20 mm Hg in SHR, but did not affect blood pressure in WKY rats. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Endothelium-dependent relaxation induced by acetylcholine was more pronounced in normotensive than in hypertensive rats and was improved by trichlormethiazide in SHR, whereas endothelium- independent relaxation to the nitric oxide donor 3-morpholinosynonimine was comparable in all study groups. Arterial relaxation to isoproterenol also was attenuated in SHR when compared with WKY rats, and remained unaffected by trichlormethiazide in both strains. Relaxation responses induced by return of K+ to the organ bath upon precontractions elicited by K(+)-free solution were used to evaluate the function of vascular smooth muscle Na+,K(+)-adenosine 5'- triphosphatase. The maximal rate of K+ relaxation was fastest in the normotensive groups, but also was clearly faster in trichlormethiazide- treated SHR when compared with untreated SHR. Furthermore, arterial contractile force generation to KCl and norepinephrine, and vascular calcium sensitivity during stimulation with these agonists, were not affected by trichlormethiazide in either strain. The ability of arterial smooth muscle to sequester calcium was evaluated by means of caffeine- and norepinephrine-induced contractions after loading periods in different organ bath calcium concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 272, Issue 3, pp. 1223-1230, 03/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics

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