title: Discoordinate regulation of renal nitric oxide synthase isoforms in ovariectomized mRen2. Lewis rats.
abstract: Estrogen depletion markedly exacerbates hypertension in female congenic mRen2. Lewis rats, a model of tissue renin overexpression. Because estrogen influences nitric oxide synthase (NOS) and NO may exert differential effects on blood pressure, the present study investigated the functional expression of NOS isoforms in the kidney of ovariectomized (OVX) mRen2. Lewis rats. OVX-mRen2. Lewis exhibited an increase in systolic blood pressure (SBP) of 171 +/- 5 vs. 141 +/- 7 mmHg (P < 0.01) for intact littermates. Renal cortical mRNA and protein levels for endothelial NOS (eNOS) were reduced 50-60% (P < 0.05) and negatively correlated with blood pressure. In contrast, cortical neuronal NOS (nNOS) mRNA and protein levels increased 100 to 300% (P < 0.05). In the OVX kidney, nNOS immunostaining was more evident in the macula densa, cortical tubules, and the medullary collecting ducts compared with the intact group. To determine whether the increase in renal nNOS expression constitutes a compensatory response to the reduction in renal eNOS, we treated both intact and OVX mRen2. Lewis rats with the selective nNOS inhibitor L-VNIO from 11 to 15 wk of age. The nNOS inhibitor reduced blood pressure in the OVX group (185 +/- 3 vs. 151 +/- 8 mmHg, P < 0.05), but pressure was not altered in the intact group (146 +/- 4 vs. 151 +/- 4 mmHg). In summary, exacerbation of blood pressure in the OVX mRen2. Lewis rats was associated with the discoordinate regulation of renal NOS isoforms. Estrogen sensitivity in this congenic strain may involve the influence of NO through the regulation of both eNOS and nNOS.
authors.affiliation: Hypertension and Vascular Disease Center, Wake Forest University Health Sciences, Medical Center Blvd., Winston-Salem, NC 27157-1095, USA.
authors.forename: Liliya M
authors.initials: LM
authors.lastname: Yamaleyeva
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Gallagher
authors.forename: Sharon
authors.initials: S
authors.lastname: Vinsant
authors.forename: Mark C
authors.initials: MC
authors.lastname: Chappell
mesh_terms: D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis; D007668:Kidney / Q000201:enzymology*; D007672:Kidney Cortex / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D010052:Ovariectomy; D051381:Rats; D011917:Rats, Inbred Lew; D012083:Renin / Q000097:blood
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D009566:Nitrates; D000804:Angiotensin II; D009569:Nitric Oxide; D000450:Aldosterone; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012083:Renin