title: Effect of losartan on renal microvasculature during chronic inhibition of nitric oxide visualized by micro-CT.
abstract: Chronic inhibition of nitric oxide (NO) synthase with the competitive l-arginine analog NG-nitro-l-arginine methyl ester (l-NAME) leads to an elevated systemic blood pressure and reduction in renal blood flow without significant changes in urinary sodium and water excretion. Simultaneous administration of ANG II AT1 receptor antagonist losartan and l-NAME prevents the alterations in blood pressure and renal hemodynamics. Microcomputed tomography (micro-CT) was used to investigate the role of ANG II in the changes of renal microvasculature during chronic NO inhibition. Sprague-Dawley rats were given l-NAME with or without AT1 receptor antagonist losartan (40 mg. kg-1. day-1 each) in their drinking water for 19 days. Kidneys from each group (control, l-NAME-, and l-NAME + losartan-treated rats) were perfusion-fixed in situ, infused with a silicon-based polymer containing lead chromate, and scanned by micro-CT. The microvasculature in the reconstructed three-dimensional renal images was studied using computerized analytic techniques. Kidneys of l-NAME-treated rats had significantly fewer normal glomeruli (28,824 +/- 838) than those of control rats (36,266 +/- 3,572). Losartan normalized the number to control values (34,094 +/- 1,536). The amount of vasculature in the cortex, outer medulla, and inner medulla of l-NAME-treated rats was about two-thirds that of control rats; losartan normalized the values to control levels. These data indicate that chronic treatment with the NO synthase inhibitor l-NAME produces a generalized rarefaction of renal capillaries. Because simultaneous AT1 receptor blockade abolished those changes, the data suggest that the reduction in vasculature is mediated by ANG II through AT1 receptors.
authors.affiliation: Department of Physiology and Biophysics, Mayo Clinic and Foundation, Rochester 55905, USA.
authors.forename: Loudes A
authors.initials: LA
authors.lastname: Fortepiani
authors.forename: M Clara Ortiz
authors.initials: MC
authors.lastname: Ruiz
authors.forename: Federico
authors.initials: F
authors.lastname: Passardi
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bentley
authors.forename: Joaquin
authors.initials: J
authors.lastname: Garcia-Estan
authors.forename: Erik L
authors.initials: EL
authors.lastname: Ritman
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Romero
mesh_terms: D000792:Angiography; D000804:Angiotensin II / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001808:Blood Vessels / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000000981:diagnostic imaging / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014057:Tomography, X-Ray Computed
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester