Effects of Indapamide, a Thiazide-Like Diuretic, on Structure of Cerebral Arterioles in Hypertensive Rats

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 43; no. 5; pp. 1092 - 1097
• Main Authors: Chillon, Jean-Marc, Baumbach, Gary L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-05-2004; Hagerstown, MD Lippincott
• Subjects: Animals; Antihypertensive agents; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Antihypertensive Agents - therapeutic use; Arterial hypertension. Arterial hypotension; Arterioles - drug effects; Arterioles - pathology; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Brain - blood supply; Brain - drug effects; Cardiology. Vascular system; Cardiovascular system; Diuretics - administration & dosage; Diuretics - pharmacology; Diuretics - therapeutic use; Dose-Response Relationship, Drug; Experimental diseases; Hypertension - drug therapy; Hypertension - pathology; Hypertrophy; Indapamide - administration & dosage; Indapamide - pharmacology; Indapamide - therapeutic use; Male; Medical sciences; Nitric Oxide - physiology; Pharmacology. Drug treatments; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Hypertension; Scanning electron microscopy; remodeling; Sulfonamide; Indapamide; Rat; hypertrophy; Low dose; Rodentia; Cardiovascular disease; Stress; Encephalon; Diuretic; Vertebrata; Mammalia; Treatment; Animal; Antihypertensive agent; Thiazide; Indole derivatives; High dose; Comparative study
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000122874.21730.81

ABSTRACT—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 μm in WKY and 1439±40 μm 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 μm). Treatment with either dose of indapamide failed to increase external diameter in cerebral arterioles of SHR (89±4 and 92±4 μm, respectively, versus 103±6 μm in WKY and 87±4 μm 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.