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Comparison of the AT1-receptor blockers candesartan, irbesartan and losartan for inhibiting renal microvascular constriction

Laboratory for Physiology, Vrije Universitet, w.van_rodijnen. physiol{at}med.vu.nl

Ton A van Lambalgen

Laboratory for Physiology, Vrije Universitet

Marco E van Teijlingen

Laboratory for Physiology, Vrije Universitet

Geert-Jan Tangelder

Laboratory for Physiology, Vrije Universitet

Piet M ter Wee

Department of Nephrology, Institute for Cardiovascular Research (ICaR-VU), Vrije Universiteit, Amsterdam, The Netherlands

Angiotensin II (Ang II) type 1 (AT₁) receptor blockers differ in their affinity for the AT₁-receptor, suggesting a dissimilar potency for inhibiting Ang II-induced vascular constriction. In the present study, we compared the effects of candesartan, irbesartan and losartan on the renal microvascular constriction to locally-formed Ang II, using isolated, perfused hydronephrotic rat kidneys. Addition of 1 nmol/L angiotensin I (Ang I, the precursor of Ang II) significantly reduced the diameters of interlobular arteries (ILAs; -47.6±2.6%), afferent arterioles (AAs; -43.6±2.3%) and efferent arterioles (EAs; -31.6±2.4%). Candesartan and irbesartan were more potent in antagonising the constriction to Ang I than losartan. By contrast, candesartan and irbesartan differed only slightly in potency. After a washing period of 60 minutes with drug-free medium, a second application of Ang I failed to induce vasoconstriction only in candesartan-treated kidneys. Pretreatment of hydronephrotic kidneys with candesartan, to further explore its antagonistic properties, shifted the dose-response curves of Ang II approximately 2 log units to the right without reducing the maximal Ang II-induced constriction of ILAs, AAs or EAs. Additionally, dose-response curves of Ang II were similar after short (10 minutes) and prolonged (60 minutes) preincubation with candesartan. Our findings indicate that candesartan and irbesartan are more potent inhibitors of renal microvascular constriction to locally-formed Ang II than losartan. The inhibitory effect of candesartan is more prolonged, suggesting a slow dissociation from the AT₁-receptor. Additionally, candesartan was found to block the Ang II-induced constriction of renal microvessels in a surmountable manner.

Key Words: isolated perfused hydronephrotic rat kidney • renal microvessels • AT1 antagonists • candesartan • irbesartan • losartan

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S204-S210 (2001)
DOI: 10.1177/14703203010020013601


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