Roles of Nitric Oxide and Oxidative Stress in the Regulation of Blood Pressure and Renal Function in Prehypertensive Ren-2 Transgenic Rats

Abstract

Aims: The present study was performed to evaluate the role of nitric oxide (NO) and its interaction with superoxide anion (O₂^–) in the regulation of blood pressure (BP) and renal function during the developmental phase of hypertension in Ren-2 transgenic rats (TGR). The first aim was to compare BP and renal functional responses to acute NO synthase (NOS) inhibition achieved by intravenous (i.v.) infusion of N^ω-nitro-L-arginine-methyl ester (L-NAME) in prehypertensive heterozygous TGR and in transgene-negative Hannover Sprague-Dawley (HanSD) rats. The second aim was to evaluate whether scavenging of O₂^– by infusion of the superoxide dismutase mimetic tempol increases NO bioavailability which therefore should augment BP and renal functional responses to L-NAME. Methods: Rats were anesthetized, prepared for clearance experiments and BP and renal functional responses were evaluated in response to i.v. L-NAME administration (20 µg·100 g^–1·min^–1) without or with tempol pretreatment (i.v., 300 µg·100 g^–1·min^–1). In renal cortical tissue, nitrotyrosine protein expression was assessed by immunoblotting as marker of O₂^– production and urinary 8-epi-PGF_2α excretion as marker of intrarenal oxidative stress was assessed by enzyme immunoassay. Results: BP, glomerular filtration rate (GFR), renal plasma flow (RPF) and sodium excretion were similar in TGR and HanSD. L-NAME infusion induced greater increases in BP in TGR than in HanSD (+42 ± 4 vs. +25 ± 3 mm Hg, p < 0.05). In the absence of a significant change in GFR, L-NAME caused similar decreases in RPF (–32 ± 6 and –25 ± 4%, p < 0.05) in TGR and HanSD. Despite significantly higher renocortical expression of nitrotyrosine and urinary 8-epi-PGF_2α excretion in TGR than in HanSD, pretreatment with tempol did not augment the rise in BP and the decrease in RPF induced by L-NAME. Conclusions: The greater BP response to L-NAME in TGR suggests that prehypertensive TGR exhibit an enhanced NO activity in the systemic vasculature as compared with HanSD. Despite increased intrarenal oxidative stress in TGR, the dependency of the intrarenal vascular tone on NO appears to be similar in TGR and HanSD. The lack of a compensatory increase in renal NO activity may partially account for the enhanced renal vascular response to ANG II present in TGR.

Role of nitric oxide in regulating epidermal permeability barrier function

“…9 In contrast, blockade of NO synthesis decreases T regulatory cells, worsens renal damage and increases blood pressure in rats. [10][11][12] Studies have also demonstrated an important regulatory role for NO in cutaneous functions. Previous studies showed that NO stimulates keratinocyte migration in vitro, 13 while deficiency in iNOS delays cutaneous wound healing.…”

D5 dopamine receptor decreases NADPH oxidase, reactive oxygen species and blood pressure via heme oxygenase-1

“…16 Increased production of ROS has been reported in human essential hypertension, as well as in animal models of genetic and acquired hypertension. 13,17–21 Increased levels of ROS are caused not only by enhanced oxidant activity, but also by deficient activity of antioxidant enzymes, for example, heme oxygenase (HO). 22–26 …”