title: A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats.
abstract: 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.
authors.affiliation: Department of Nephrology and Hypertension F03.223, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Maarten P
authors.initials: MP
authors.lastname: Koeners
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
authors.forename: Dionne M
authors.initials: DM
authors.lastname: van der Giezen
authors.forename: Roel
authors.initials: R
authors.lastname: Goldschmeding
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D006973:Hypertension / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D007668:Kidney / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D011507:Proteinuria / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
chemical_list: D020030:Nitric Oxide Donors; D012964:Sodium; D008981:Molsidomine