Effect of ANG II type I receptor antagonist and ACE inhibitor on vitamin D receptor-null mice.
We recently showed that vitamin D receptor (VDR) inactivation results in deregulated stimulation of the renin-angiotensin system (RAS). To address further the relation between RAS activation and the abnormalities in electrolyte and volume homeostasis, we studied the effect of the ANG II type I receptor antagonist losartan and the angiotensin-converting enzyme inhibitor captopril on VDR-null mice. Treatment with losartan or captopril normalized the water intake and urine excretion of VDR-null mice. However, the increase in salt excretion in VDR-null mice was not affected by either drug, suggesting that this abnormality is independent of the RAS. Northern blot and immunohistochemical analyses revealed that both drugs caused a drastic stimulation of renin expression in wild-type and VDR-null mice, but renin expression remained much higher in the treated VDR-null mice than in the treated wild-type mice, suggesting that the ANG II feedback mechanism remains intact in the mutant mice. These data firmly established a causative relation between RAS overstimulation and the abnormal volume homeostasis in VDR-null mice and demonstrated that vitamin D repression of renin expression is independent of the ANG II feedback regulation in vivo.
Kong
Juan
J
Dept. of Medicine, University of Chicago, MC 4076, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
Li
Yan Chun
YC
D000450:Aldosterone / Q000097:blood / Q000652:urine; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D044140:Receptor, Angiotensin, Type 1; D018167:Receptors, Calcitriol / Q000235:genetics*; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012492:Salts / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism; D014867:Water / Q000378:metabolism; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D018167:Receptors, Calcitriol; D012492:Salts; D014867:Water; D000450:Aldosterone; D002216:Captopril; D012083:Renin; D019808:Losartan