Effect of losartan on functional and structural properties of conduit atery wall in young spontaneously hypertensive rats

Abstract The effect of losartan on systolic blood pressure (SBP), function and structure of thoracic aorta and mesenteric artery was examined. Four-week-old Wistar rats, spontaneously hypertensive rats (SHR), and SHR treated with losartan (20 mg/kg/day for 5 weeks) were used. SBP was measured by the tail-cuff method weekly. Isometric contraction of aortal rings and neurogenic contractions of mesenteric artery were studied in organ baths. For in vivo investigation after anesthesia, carotid artery was cannulated for SBP measurement and jugular vein for drug administration. Then thoracic aorta was processed according to electron microscopy procedure. In SHR (9-week-old) SBP and relative heart weight were increased, acetylcholine induced relaxation of phenylephrine-precontracted aortal rings was reduced compared to Wistar rats. In losartan treated SHR SBP and relative heart weight were lowered. Impairment of acetylcholine-induced relaxation was prevented and neurogenic responses of mesenteric artery were suppressed. In vivo administration of acetylcholine (0.1µg, 1µg, 10µg) evoked similar decrease of SBP in SHR and Wistar rats. In losartan treated SHR the decrease of SBP was larger than in SHR and Wistar rats. Wall thickness (WT) and cross-sectional area (CSA) of the aorta in SHR were decreased compared to Wistar rats; inner diameter (ID) and WT/ID ratio were not changed. In losartan treated SHR ID was increased and WT/ID decreased while WT and CSA were not changed. Conclusion: Losartan administered to SHR (i) reduced SBP, (ii) prevented impairment of endothelium-dependent relaxation, (iii) improved integrated responses to acetylcholine, and (iv) reduced structural changes in the aortic wall.

Keywords Hypertension, Conduit artery, Losartan, Neurogenic contraction, Structure.

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