Chlorthalidone reduces vascular hyperresponsiveness in DOCA-salt hypertensive rats.
The mechanisms of anti-hypertensive effect of diuretics remain unknown. The purpose of this study was to test the hypothesis that long-term treatment with chlorthalidone decreases the responsiveness of resistance vessels to neurohormones. The study was performed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats with and without treatment with chlorthalidone (Chlor. 8 mg/day, for 20 days). Resting mean arterial pressure in freely moving state was significantly reduced in DOCA-salt-Chlor rats when compared to DOCA-salt rats (116 +/- 3 vs 147 +/- 7 mmHg, respectively). Chlorthalidone treatment reduced the high plasma sodium content observed in DOCA-salt rats to the same levels observed in normotensive control groups. Results obtained in isolated perfused mesenteric arteries showed: a) the increase in perfusion pressure elicited by norepinephrine (NE), serotonin (SE) and vasopressin (VP) was significantly greater in DOCA-salt than in DOCA-salt + Chlor rats or control normotensive rats; b) the endothelium removal increased the pressor responses to NE, SE and VP in a similar way in all groups. These data provide evidence that long-term chlorthalidone treatment reduces vascular hyperresponsiveness to these neurohormones. In addition, these results indicate that this reduction in vascular hyperresponsiveness, associated with a decrease in extracellular sodium level, could be a possible mechanism by which the diuretics reduce the high blood pressure.
Cabral
A M
AM
Dept. Physiological Sciences, UFES, Brazil.
Musso
M N
MN
Bissoli
N S
NS
Carvalhinho
F B
FB
Vasquez
E C
EC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002752:Chlorthalidone / Q000494:pharmacology*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D012964:Sodium / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D012701:Serotonin; D003900:Desoxycorticosterone; D012964:Sodium; D002752:Chlorthalidone; D009638:Norepinephrine