Key result
Candesartan and irbesartan were more potent inhibitors of renal microvascular constriction to locally-formed Ang II than losartan, with candesartan exhibiting a more prolonged inhibitory effect.
Why the study?
Do candesartan and irbesartan inhibit renal microvascular constriction more potently than losartan in isolated rat kidneys?
Do candesartan and irbesartan inhibit renal microvascular constriction more potently than losartan in isolated rat kidneys?
Candesartan and irbesartan are more potent inhibitors of Ang II-induced renal microvascular constriction than losartan, with candesartan exhibiting a more prolonged effect suggesting slow receptor dissociation.
Answers are grounded in this paper and cite their sources.
Does not warrant preferential ARB selection in patients; leaves open whether potency differences affect renal outcomes in humans.
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.
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Rodijnen et al. (2001) studied Renal microvascular constriction. Candesartan and irbesartan vs. Losartan was evaluated on Renal microvascular constriction to locally-formed Ang II. Candesartan and irbesartan were more potent inhibitors of renal microvascular constriction to locally-formed Ang II than losartan, with candesartan exhibiting a more prolonged inhibitory effect.
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