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This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 294/6/R1847    most recent 00073.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Koeners, M. P. Articles by Joles, J. A. Search for Related Content PubMed PubMed Citation Articles by Koeners, M. P. Articles by Joles, J. A.

RENAL HEMODYNAMICS AND CARDIORENAL INTEGRATION

A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats

¹Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands; ²Division of Nephrology and Immunology/Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; and ³Department of Pathology, University Medical Center, Utrecht, The Netherlands

Submitted 31 January 2008 ; accepted in final form 4 April 2008

Enhancing perinatal nitric oxide (NO) availability persistently reduces blood pressure in spontaneously hypertensive rats. We hypothesize that this approach can be generalized to other models of genetic hypertension, for instance those associated with renal injury. Perinatal exposure to the NO donor molsidomine was studied in fawn-hooded hypertensive (FHH) rats, a model of mild hypertension, impaired preglomerular resistance, and progressive renal injury. Perinatal molsidomine increased urinary NO metabolite excretion at 8 wk of age, i.e., 4 wk after treatment was stopped (P < 0.05). Systolic blood pressure was persistently reduced after molsidomine (42-wk females: 118 ± 3 vs. 141 ± 5 and 36-wk males: 139 ± 4 vs. 158 ± 4 mmHg; both P < 0.001). Perinatal treatment decreased glomerular filtration rate (P < 0.05) and renal blood flow (P < 0.01) and increased renal vascular resistance (P < 0.05), without affecting filtration fraction, suggesting persistently increased preglomerular resistance. At 4 wk of age natriuresis was transiently increased by molsidomine (P < 0.05). Molsidomine decreased glomerulosclerosis (P < 0.05). Renal blood flow correlated positively with glomerulosclerosis in control (P < 0.001) but not in perinatally treated FHH rats. NO dependency of renal vascular resistance was increased by perinatal molsidomine. Perinatal enhancement of NO availability can ameliorate development of hypertension and renal injury in FHH rats. Paradoxically, glomerular protection by perinatal exposure to the NO donor molsidomine may be due to persistently increased preglomerular resistance. The mechanisms by which increased perinatal NO availability can persistently reprogram kidney function and ameliorate hypertension deserve further study.

proteinuria; renal hemodynamics; glomerulosclerosis