Effects of thiazide diuretic on vascular eicosanoid system of spontaneously hypertensive rats.
To assess the role of the vascular eicosanoid system in thiazide therapy, we examined the aortic eicosanoid system of spontaneously hypertensive rats (SHR) treated with trichloromethiazide for 2 weeks. The blood pressure reduction caused by the thiazide treatment was associated with a significant decrease in vascular vasodepressor prostacyclin (PGI2) generation, whereas neither nifedipine nor captopril treatment lowered vascular PGI2 generation. The thiazide diuretic directly lowered PGI2 synthase activity in cultured vascular smooth muscle cells (VSMC), thereby decreasing PGI2 generation in the VSMC and probably in the aortic wall. This direct inhibitory effect on vascular PGI2 generation was not observed with either furosemide or indapamide. Thus, vascular PGI2 generation is reduced with trichloromethiazide, partly through its direct inhibition of PGI2 synthase; this has possible relevance to the non-beneficial effects of thiazide diuretics on the vascular sclerotic changes.
Numabe
A
A
Department of Medicine, Dokkyo University School of Medicine, Tochigi, Japan.
Uehara
Y
Y
Hirawa
N
N
Takada
S
S
Yagi
S
S
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004232:Diuretics; D011464:Epoprostenol / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D014237:Trichlormethiazide / Q000627:therapeutic use
D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D014237:Trichlormethiazide