The contribution of nitric oxide to cardiovascular status and responses to vasodilators in conscious, hypertensive, transgenic ((mRen‐2)27) rats

Gardiner, Sheila M.; March, J E; Kemp, P.A.; Bennett, T.

doi:10.1038/sj.bjp.0701838

Cited by 10 publications

(17 citation statements)

References 60 publications

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“…These findings suggest that prehypertensive TGR exhibit an enhanced NO activity in the systemic vasculature but a relative independency of the intrarenal vascular tone on NO. This concept is supported by observations by Gardiner et al [20,21] who demonstrated that there is no evidence for an increased NO activity in TGR compared with HanSD and that NO does not act as a buffer to antagonize the vasoconstrictor actions of ANG II. In accordance with previous findings that responses of urine flow and sodium excretion to NOS inhibition are influenced by the concomitant increases in BP [11][12][13][14], i.e.…”

Section: Discussionsupporting

confidence: 73%

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

Vaněčková

Kramer

Novotná

et al. 2005

Kidney Blood Press Res

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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.

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Section: Discussionsupporting

confidence: 73%

“…On the other hand, it has been shown that acute NOS inhibition elicited similar BP responses in TGR and HanSD [20,21]. In addition, reduced endotheliumdependent vasorelaxation has been reported in aortic ring preparations from male TGR [22].…”

Section: Introductionmentioning

confidence: 87%

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

Vaněčková

Kramer

Novotná

et al. 2005

Kidney Blood Press Res

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“…In the second part of the study, we chose to infuse the NOS inhibitors, and compare their effects on a range of vasodilators, some of the responses to which we have previously shown to be influenced by L ‐NAME (Gardiner et al ., 1991b; 1992; 1998).…”

Section: Discussionmentioning

confidence: 99%

“…The order of administration was randomised between animals within the groups, with at least 10 min between each substance to allow return to baseline values. The doses of vasodilators were chosen on the basis of previous experiments (Gardiner et al ., 1991b; Randall et al ., 1996; Gardiner et al ., 1998), which showed that they produced robust, steady‐state responses.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, we hypothesised that a comparison of the influence of SMTC and L ‐NAME on the effects of a range of vasodilators might reveal differences that would help in distinguishing actions due to inhibition of nNOS vs eNOS. Thus, in additional experiments, we assessed the effects of SMTC and L ‐NAME on responses to acetylcholine, which causes L ‐NAME‐sensitive renal vasodilatation in conscious rats (Gardiner et al ., 1991b); bradykinin, which causes mesenteric vasodilatation that is resistant to L ‐NAME (Randall et al ., 1996); salbutamol, which causes L ‐NAME‐sensitive, β 2 ‐adrenoceptor‐mediated, hindquarters vasodilatation (Gardiner et al ., 1991b); and sodium nitroprusside, which causes enhanced mesenteric vasodilatation in the presence of L ‐NAME, possibly due to upregulation of guanylyl cyclase sensitivity (Gardiner et al ., 1998). Some of this work has been presented to the British Pharmacological Society (Wakefield et al ., 2002a,2002b,2002c).…”

Section: Introductionmentioning

confidence: 99%

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Comparative regional haemodynamic effects of the nitric oxide synthase inhibitors, S‐methyl‐L‐thiocitrulline and L‐NAME, in conscious rats

Wakefield

March

Kemp

et al. 2003

British J Pharmacology

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1 The regional haemodynamic effects of the putative nNOS inhibitor, S-methyl-l-thiocitrulline (SMTC), were compared with those of the nonselective NOS inhibitor, N G -nitro-l-arginine methyl ester (l-NAME), in conscious, male Sprague -Dawley rats. 2 SMTC (0.3 mg kg À1 bolus) produced a significant, short-lived, pressor effect associated with renal, mesenteric and hindquarters vasoconstriction; the same dose of l-NAME did not affect mean blood pressure (BP), although it caused bradycardia and mesenteric vasoconstriction.3 At the highest dose tested (10 mg kg À1 ), l-NAME produced a significantly greater bradycardia and fall in mesenteric vascular conductance than SMTC, although the initial pressor response to SMTC was greater, but less sustained, than that to l-NAME. 4 Infusion of SMTC or l-NAME (3 mg kg À1 h À1) induced rises in BP and falls in renal, mesenteric and hindquarters vascular conductances, but the effects of l-NAME were greater than those of SMTC, and l-NAME also caused bradycardia. 5 The renal vasodilator response to acetylcholine was markedly attenuated by infusion of l-NAME, but unaffected by SMTC. The hindquarters vasodilatation induced by salbutamol was attenuated by l-NAME, but not by SMTC. The mesenteric vasodilator response to bradykinin was modestly enhanced by SMTC, but not by l-NAME. The depressor and renal, mesenteric and hindquarters vasodilator responses to sodium nitroprusside were enhanced by l-NAME, whereas SMTC modestly enhanced the hypotensive and renal vasodilator effects of sodium nitroprusside, but attenuated the accompanying tachycardia. 6 The results are consistent with the cardiovascular effects of low doses of SMTC being attributable to nNOS inhibition.

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The Effect of Nitric Oxide Inhibition on Blood Pressure Depends on Rat Strain

Forster¹,

Beebe²,

Wang³

et al. 2001

Journal of Surgical Research

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The contribution of nitric oxide to cardiovascular status and responses to vasodilators in conscious, hypertensive, transgenic ((mRen‐2)27) rats

Cited by 10 publications

References 60 publications

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

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

Comparative regional haemodynamic effects of the nitric oxide synthase inhibitors, S‐methyl‐L‐thiocitrulline and L‐NAME, in conscious rats

The Effect of Nitric Oxide Inhibition on Blood Pressure Depends on Rat Strain

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