Effects of indapamide, a thiazide-like diuretic, on structure of cerebral arterioles in hypertensive rats.
We examined the effects of indapamide, a thiazide-like diuretic, on cerebral arterioles in spontaneously hypertensive rats (SHR). The structure and mechanics of cerebral arterioles were examined in untreated Wistar Kyoto rats (WKY) and SHR that were untreated or treated for 3 months with a low (1 mg/kg per day) or a high (10 mg/kg per day) dose of indapamide. We measured pressure, diameter, and cross-sectional area of the vessel wall (CSA) in maximally-dilated (EDTA) cerebral arterioles. Treatment of SHR with the high dose of indapamide normalized cerebral arteriolar mean pressure (62+/-4 [mean+/-SEM] versus 59+/-3 mm Hg in WKY and 88+/-6 mm Hg in untreated SHR; P<0.05), pulse pressure (13+/-1 versus 10+/-1 mm Hg in WKY and 20+/-1 mm Hg in untreated SHR; P<0.05), and CSA (1080+/-91 versus 1100+/-48 microm2 in WKY and 1439+/-40 microm2 in untreated SHR; P<0.05). In contrast, treatment of SHR with the low dose of indapamide did not normalize arteriolar mean (72+/-3) and pulse pressure (20+/-1 mm Hg), but did normalize CSA (1091+/-52 microm2). Treatment with either dose of indapamide failed to increase external diameter in cerebral arterioles of SHR (89+/-4 and 92+/-4 microm, respectively, versus 103+/-6 microm in WKY and 87+/-4 microm in untreated SHR). Finally, treatment with indapamide attenuated the rightward shift of the stress-strain curve in SHR, suggesting that treatment with indapamide attenuated increases in distensibility of cerebral arterioles in SHR. These findings suggest that, whereas thiazide-like diuretics may not attenuate eutrophic inward remodeling of cerebral arterioles in SHR, they may attenuate hypertrophic inward remodeling via a mechanism unrelated to their pressor effects.
Laboratory of Cardiovascular Pharmacology, Faculty of Pharmacy, University Henri Poincaré-Nancy, France.
Jean-Marc
JM
Chillon
Gary L
GL
Baumbach
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D006984:Hypertrophy; D007190:Indapamide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D004232:Diuretics; D009569:Nitric Oxide; D007190:Indapamide