Endothelial Dysfunction of Resistance Arteries of Spontaneously Hypertensive Rats

Fu-Xiang, D; Jameson, Michael; Skopec, J.; Diederich, A.; Diederich, D.

doi:10.1097/00005344-199204002-00053

Cited by 45 publications

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“…Endothelium-dependent contracting factors have also been described in a number of different vascular beds including the aorta (Luscher & Vanhoutte, 1986;Diederich et al, 1990;Dohi et al, 1990;Kato et al, 1990) and renal arcuate arteries of spontaneously hypertensive rats (SHR) (Fu-Xiang et al, 1992). Similar factors have also been described in WistarKyoto (WKY) rats, (Diederich et al, 1989;Koga et al, 1989;Kato et al, 1990) although not consistently.…”

Section: Introductionmentioning

confidence: 94%

“…In the aorta of both WKY and SHR the contracting factor appears to be either I Author for correspondence. prostaglandin H2 (Kato et al, 1990;Fu-Xiang et al, 1992) or thromboxane A2 (Lin & Nasjletti, 1991); however, in mesenteric resistance vessels from SHR, Jameson et al (1993) have proposed that cyclo-oxygenase-generated superoxide anions are responsible. Kanner et al (1992) have demonstrated that nitric oxide inhibits lipid oxidation by both lipoxygenase and cyclooxygenase, raising the possibility of an inter-relationship between the endothelium-derived nitric oxide vasodilator system and endothelium-derived vasoconstrictor prostanoids.…”

Section: Introductionmentioning

confidence: 99%

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Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid

Johns

Michael

et al. 1994

British J Pharmacology

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1 We have examined the effects of nitric oxide inhibition, indomethacin and the dual lipoxygenase/ cyclo-oxygenase inhibitor, 3-amino-l-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C), on the responses of small mesenteric arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2 Noradrenaline, potassium chloride and endothelin-l caused concentration-dependent contraction of small mesenteric arteries. Indomethacin (14 iM) attenuated the contractile response to both noradrenaline and potassium chloride. The inhibitory action of indomethacin persisted in vessels treated with CHAPS. 3 Acetylcholine produced concentration-dependent relaxation in these vessels. Indomethacin (14JM) had no significant effect on the acetylcholine concentration-response relationship. 4 NG-nitro-L-arginine methyl ester (L-NAME, 100 LM) potentiated the contractile response to both noradrenaline and potassium chloride and inhibited acetylcholine-induced relaxation. Indomethacin attenuated the effects of L-NAME. 5 BW755C inhibited the contractile response to noradrenaline and potassium chloride but not to endothelin-1. The inhibitory effects of BW755C persisted in the presence of indomethacin and in vessels treated with CHAPS. 6 BW755C enhanced endothelium-dependent relaxation, as assessed by the response to acetylcholine. In the presence of indomethacin, BW755C produced a shift to the right of the concentration-response curve to acetylcholine. 7 Inhibition of nitric oxide synthase with L-NAME, reversed the inhibitory effect of BW755C on noradrenaline-and potassium-induced contraction. L-NAME and BW755C in combination resulted in a shift to the right of the concentration-response curve to acetylcholine. 8 Sodium nitroprusside produced concentration-dependent relaxation of the vessels. Endothelium removal reduced the maximum relaxation to nitroprusside. BW755C did not alter the response to sodium nitroprusside in vessels with or without endothelium. 9 These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of small mesenteric arteries with noradrenaline and potassium chloride: a cyclo-oxygenase product and a lipoxygenase product both of which appear to be largely endothelium-independent.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid

Johns

Michael

et al. 1994

British J Pharmacology

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“…Nitric oxide is known to be tonically released and has major influences on regional haemodynamics in particular within the kidney, although the exact site of action remains contentious (Tolins et al, 1990;Radermacher et al, 1990). Endothelium-dependent contracting factors have also been described in a number of different vascular beds including the aorta (Luscher & Vanhoutte, 1986;Diederich et al, 1990; Dohi et al, 1990; Kato et al, 1990) and renal arcuate arteries of spontaneously hypertensive rats (SHR) (Fu-Xiang et al, 1992). Similar factors have also been described in WistarKyoto (WKY) rats, (Diederich et al, 1989;Koga et al, 1989; Kato et al, 1990) although not consistently.…”

Section: Introductionmentioning

confidence: 99%

“…oxygenase-dependent (Diederich et al, 1990;Lischer et al, 1990) but the compounds responsible vary depending upon the species and vascular bed studied. In the aorta and intrarenal arteries of both WKY and SHR the contracting factor appears to be either prostaglandin H2 (Kato et al, 1990;Fu-Xiang et al, 1992) or thromboxane A2 (Lin & Nasjletti, 1991).…”

Section: Introductionmentioning

confidence: 99%

Relative roles of nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid in the contractile responses of rat renal arcuate arteries

Richards

Michael

et al. 1994

British J Pharmacology

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1 We have examined the effects of inhibition of nitric oxide synthase, cyclo-oxygenase and lipoxygenase on the responses of renal arcuate arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-l, acetylcholine and sodium nitroprusside. 2 Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of the vessels. Indomethacin (14 fLM) attenuated the contractile response to noradrenaline and to potassium chloride. The inhibitory effect of indomethacin persisted following endothelial removal. 3 Acetylcholine produced concentration-dependent relaxation of the vessels which was potentiated by indomethacin (14 gM). 4 NG-nitro-L-arginine methyl ester (L-NAME, 100 gM) did not affect the contractile response to either noradrenaline or potassium chloride but abolished relaxation to acetylcholine. In addition, L-NAME abolished the affects of indomethacin on acetylcholine-induced relaxation and noradrenaline-and potassium chloride-induced contraction. 5 BWC755C attenuated noradrenaline and potassium chloride-induced contraction. This effect persisted in the presence of indomethacin. 6 In vessels pretreated with CHAPS, BW755C inhibited both noradrenaline and potassium chlorideinduced contraction. In these vessels BW755C had no additional inhibitory effect to indomethacin on noradrenaline-and potassium-induced contraction.7 Inhibition of nitric oxide synthase with L-NAME (1001iM) attenuated the effect of BW755C on noradrenaline-and potassium-induced contraction. 8 BW755C alone did not affect endothelium-dependent relaxation as assessed by the response to acetylcholine. However, in the presence of indomethacin, BW755C inhibited acetylcholine-induced relaxation. 9 BW755C did not affect endothelium-independent relaxation as assessed by the response to sodium nitroprusside in vessels with or without endothelium. 10 These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of renal arcuate arteries with noradrenaline and potassium chloride. A cyclooxygenase product which appears to be endothelium-independent and the other an endotheliumdependent lipoxygenase product.

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“…In a model of genetic hypertension in the rat, the spontaneously hypertensive rat (SHR), abnormalities in synthesis of NO, expression of the NO-synthesizing enzymes, or both have been described both in vitro and in vivo, but with conflicting results. Thus, several studies have been performed to provide evidence of impaired vasodilation in response to acetylcholine, an effect mediated by endothelium-derived relaxing factor or NO, decreased eNOS expression, or decreased NO synthesis in SHR (5)(6)(7)(8)(9)(10)(11). These abnormalities are present as early as 5 wk of age, a period before the development of hypertension (7).…”

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confidence: 99%

Impaired Regulation of Renal Oxygen Consumption in Spontaneously Hypertensive Rats

Adler

Huang

2002

Journal of the American Society of Nephrology

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Abstract. Abnormalities of nitric oxide (NO) and oxygen radical synthesis and of oxygen consumption have been described in the spontaneously hypertensive rat (SHR) and may contribute to the pathogenesis of hypertension. NO plays a role in the regulation of renal oxygen consumption in normal kidney, so the response of renal cortical oxygen consumption to stimulators of NO production before and after the addition of the superoxide scavenging agent tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) was studied. Baseline cortical oxygen consumption was similar in SHR and Wistar-Kyoto (WKY) rats (SHR: 600 Ϯ 55 nmol O 2 /min per g, WKY: 611 Ϯ 51 nmol O 2 /min per g, P Ͼ 0.05). Addition of bradykinin, enalaprilat, and amlodipine decreased oxygen consumption significantly less in SHR than WKY (SHR: bradykinin Ϫ13.9 Ϯ 1.9%, enalaprilat Ϫ15.3 Ϯ 1.6%, amlodipine Ϫ11.9 Ϯ 0.7%; WKY: bradykinin Ϫ22.8 Ϯ 1.0%, enalaprilat Ϫ24.1 Ϯ 2.0%, amlodipine Ϫ20.7 Ϯ 2.3%; P Ͻ 0.05), consistent with less NO effect in SHR. Addition of tempol reversed the defects in responsiveness to enalaprilat and amlodipine, suggesting that inactivation of NO by superoxide contributes to decreased NO availability. The response to an NO donor was similar in both groups and was unaffected by the addition of tempol. These results demonstrate that NO availability in the kidney is decreased in SHR, resulting in increased oxygen consumption. This effect is due to enhanced production of superoxide in SHR. By lowering intrarenal oxygen levels, reduced NO may contribute to susceptibility to injury and renal fibrosis. Increasing NO production, decreasing oxidant stress, or both might prevent these changes by improving renal oxygenation.Nitric oxide (NO) plays an important role in regulation of vascular tone. Absence of the NO generating enzyme endothelial nitric oxide synthase (eNOS) or impairment of NO production leads to hypertension in animal models and can increase vascular tone in humans (1-4). In a model of genetic hypertension in the rat, the spontaneously hypertensive rat (SHR), abnormalities in synthesis of NO, expression of the NO-synthesizing enzymes, or both have been described both in vitro and in vivo, but with conflicting results. Thus, several studies have been performed to provide evidence of impaired vasodilation in response to acetylcholine, an effect mediated by endothelium-derived relaxing factor or NO, decreased eNOS expression, or decreased NO synthesis in SHR (5-11). These abnormalities are present as early as 5 wk of age, a period before the development of hypertension (7). However, several of these studies have shown a decreased effect of NO rather than direct evidence of decreased production.On the other hand, evidence of increased expression of NO synthesizing enzymes (eNOS and inducible NO synthase), increased NO production, or both have also been noted (12-18), both before and after the onset of hypertension. One possible explanation for this discrepancy is inactivation of NO, explaining increased production but less effect in SHR...

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Endothelial Dysfunction of Resistance Arteries of Spontaneously Hypertensive Rats

Cited by 45 publications

References 0 publications

Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid

Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid

Relative roles of nitric oxide and cyclo‐oxygenase and lipoxygenase products of arachidonic acid in the contractile responses of rat renal arcuate arteries

Impaired Regulation of Renal Oxygen Consumption in Spontaneously Hypertensive Rats

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