ARTERIAL FUNCTION AFTER TRICHLORMETHIAZIDE THERAPY IN SPONTANEOUSLY HYPERTENSIVE RATS

Inasmuch as the long-term influences of diuretic therapy on arterial f unction remain largely unknown, the effects of trichlormethiazide (8 m g 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 approxi mately 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 acetylch oline was more pronounced in normotensive than in hypertensive rats an d was improved by trichlormethiazide in SHR, whereas endothelium-indep endent 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 u naffected by trichlormethiazide in both strains. Relaxation responses induced by return of K+ to the organ bath upon precontractions elicite d by K+-free solution were used to evaluate the function of vascular s mooth muscle Na+,K+-adenosine 5'-triphosphatase. The maximal rate of K + relaxation was fastest in the normotensive groups, but also was clea rly faster in trichlormethiazide-treated SHR when compared with untrea ted SHR. Furthermore, arterial contractile force generation to KCI and norepinephrine, and vascular calcium sensitivity during stimulation w ith 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 contractio ns after loading periods in different organ bath calcium concentration s. The subsequent responses were lower in untreated SHR than in WKY ra ts, and caffeine-, but not norepinephrine-induced responses, were some what augmented in the treated SHR. In conclusion, the present results suggest that the long-term blood pressure lowering action of trichlorm ethiazide is accompanied by improved endothelial function and augmente d K+ relaxation (probably reflecting promoted function of vascular Na,K+-adenosine 5'-triphosphatase) in this type of genetic hypertension.