M. Kahonen et al., ARTERIAL FUNCTION AFTER TRICHLORMETHIAZIDE THERAPY IN SPONTANEOUSLY HYPERTENSIVE RATS, The Journal of pharmacology and experimental therapeutics, 272(3), 1995, pp. 1223-1230
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.