Antihypertensive effect of riboflavin analogues in spontaneously hypertensive rats.
Our study was designed to use the antimineralocorticoid property of the riboflavin analogue 7,8-dimethyl-10-(3-chlorobenzyl)isoalloxazine (CBI) to investigate the involvement of mineralocorticoids in the hypertension of the Kyoto strain of the spontaneously hypertensive rat (SHR) and Dahl salt-sensitive (S) rat. Wistar Kyoto (WKY) mildly hypertensive rats were used as controls. The administration of the riboflavin antagonist CBI at 5.0 mg/kg body weight twice weekly for 7 weeks lowered the systolic blood pressure (SBP) of the unanesthetized SHR from 188 +/- 7 mm Hg to 148 +/- 2 mm Hg (P less than 0.05). This was concurrent with a 36% and 11% decrease in iliopsoas muscle Na+ concentration and water content, respectively. The simultaneous administration of CBI and hydrochlorothiazide (HCTZ) reduced the SBP to 126 +/- 4 mm Hg (P less than 0.05). There was a profound suppressive effect of CBI on the secondary hyperaldosteronism generated by HCTZ (17.6 +/- 4.3 vs. 50.4 +/- 7.2 ng/dl, P less than 0.05), which was also reflected in the iliopsoas muscle K+ concentration. The effects of CBI on the SBP and iliopsoas muscle Na+ and K+ concentrations of age-matched WKY mildly hypertensive control rats were qualitatively similar to the effects on the SHR. In contrast to the SHR and the WKY rats, the administration of CBI for 8 weeks at 5.0 mg/kg body weight twice weekly to the Dahl S rats did not reduce their mean SBP (205 +/- 5 vs. 200 +/- 4 mm Hg, not significant). CBI treatment did not significantly decrease iliopsoas muscle Na+ concentration or water content.(ABSTRACT TRUNCATED AT 250 WORDS)
D000450:Aldosterone / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents; D005415:Flavins / Q000494:pharmacology*; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors / Q000502:physiology*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D014882:Water-Electrolyte Balance / Q000187:drug effects
D000959:Antihypertensive Agents; D005415:Flavins; D008901:Mineralocorticoids; D006852:Hydrochlorothiazide; D000450:Aldosterone; C046097:7,8-dimethyl-10-(3-chlorobenzyl)isoalloxazine