Effect of Cilazapril and Indomethacin on Endothelial Dysfunction in the Aortas of Spontaneously Hypertensive Rats

Rubanyi, Gabor M.; Kauser, Katalin; Gräser, T

doi:10.1097/00005344-199322005-00005

Cited by 26 publications

(9 citation statements)

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“…It is possible that the changes in the endothelium produced by the hypertensive state [25,26] could be responsible for the different reactivity of the hindquarters to 5-HT, this vascular bed being more reactive to vasoconstriction. According with the results previously obtained by Cheng and Shibata [17] in the hindquarters of old SHR, our experiments showed a higher increased responsiveness for the highest doses tested compared with the vasoconstrictions induced by the same doses in Wistar rats [13].…”

Section: Discussionmentioning

confidence: 99%

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Calama

Morán²,

Urbina³

et al. 2004

Pharmacology

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In this work we studied the responses and receptors involved in the effects of intra-arterial 5-hydroxytryptamine (5-HT) in the in situ autoperfused hindquarters of spontaneously hypertensive rats (SHR). Intra-arterial administration of the highest doses (50–1,000 ng/kg) produced a vasoconstrictor effect that was inhibited by ritanserin (a selective 5-HT₂ receptor antagonist), SB 206553 (a selective 5-HT_2B/2C receptor antagonist) and spiperone (a nonspecific 5-HT_1/2A receptor antagonist), and was mimicked by α-methyl-5-HT (a selective 5-HT₂ receptor agonist) and m-CPP (a selective 5-HT_2C receptor agonist), but not by the intra-arterial administration of BW 723C86, a selective 5HT_2B receptor agonist. SB 206553 and spiperone inhibited α-methyl-5HT-induced vasoconstriction in the hindquarters of SHR. Our data suggest that the vasoconstrictor response induced by 5-HT in the autoperfused hindquarters of SHR is mainly mediated by the activation of 5-HT_2A and 5-HT_2C receptors.

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Section: Discussionmentioning

confidence: 99%

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Calama

Morán²,

Urbina³

et al. 2004

Pharmacology

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“…With nitroglycerin [15] or nifedipine [16], a reduction in stiffness and with atropine an increase in stiffness [17,18] have been reported, but mere blood pressurerelated effects cannot be excluded. ACE inhibitors have been shown to directly influence the elastic properties of peripheral arterial walls to a greater extent than would be expected from their blood pressurelowering effect [19][20][21][22][23][24][25]. The aim of this study was to elucidate whether there might be an effect of an ACE inhibitor on aortic elastic properties.…”

mentioning

confidence: 99%

Influence of antihypertensive therapy with cilazapril and hydrochlorothiazide on the stiffness of the aorta

Breithaupt-Grögler¹,

Leschinger²,

Gg³

et al. 1996

Cardiovasc Drug Ther

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The purpose of this study was to examine the effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on the elastic properties of the aorta. A standard diuretic antihypertensive drug, hydrochlorothiazide, served for comparisons. Increased aortic stiffness leads to a reduction of the buffering windkessel function and is a major component in the pathophysiology of systolic hypertension, inducing an increase in left ventricular afterload and arterial pulsatile stress as well as a decrease in the subendocardial blood supply. Stiffness of arteries increases with age and blood pressure, and depends on the functional elastic structures of the aortic wall. ACE inhibitors have been shown to directly influence elastic properties of peripheral arteries. Seventeen patients with mild to moderate essential hypertension (age 45-67 years) were treated for 3 months double-blind randomized with either cilazapril (C) 5 mg daily (n = 9) or hydrochlorothiazide (HCTZ) 25 mg daily (n = 8). Aortic elastic properties were noninvasively assessed by measurement of pulse wave velocity along the aorta at rest and during isometric handgrip stress. Accelerated pulse wave velocity indicates elevated arterial stiffness and vice versa. A pressure standardized index of aortic cross-sectional distensibility (2 m) was calculated from arterial mean pressure and pulse wave velocity. Compared with pretreatment values, both therapies significantly reduced blood pressure and pulse wave velocity at rest (C: 9.4 +/- 0.9 vs. 7.7 +/- 0.7 m/sec; HcTZ: 8.9 +/- 0.3 vs. 7.8 +/- 0.4 m/sec; means +/- SEM p < 0.05). During isometric stress only C showed a significant decrease in pulse wave velocity (C: 11.3 +/- 0.8 vs. 9.1 +/- 0.8 m/sec; HCTZ: 9.9 +/- 0.5 vs. 9.0 +/- 0.5 m/sec; means +/- SEM p < 0.05). The index 2m at rest and during handgrip increased significantly (p < 0.05) after C but not after HCTZ. With cilazapril we obtained steeper slopes for the treatment-induced reductions in blood pressure and pulse wave velocity for both rest and handgrip stress values. Correlation of the data at rest and during stress revealed a direct relationship between blood pressure and pulse wave velocity. HCTZ linearly extended the relation observed before treatment toward lower values of blood pressure and corresponding pulse wave velocity without changing the relation per se. Cilazapril, in contrast, moved the relation between these variables and decelerated the pulse wave velocities to a greater extent than would have been expected from the corresponding blood pressure reduction (delta approximately 1 m/sec). These results in patients with mild to moderate essential hypertension support the idea that ACE inhibitors, in addition to reducing blood pressure, may exert an additional hemodynamic effect in improving the elastic properties of the aorta.

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“…Our findings are consistent with previous studies, which have shown that chronic hypertension is associated with endothelial dysfunction. [25][26][27][28][29][30][31] SHR has been shown to exhibit impairment in endothelium-dependent vasorelaxation. Recently, Brovkovych et al 32 demonstrated that in hypertensive SHR, endothelial dysfunction is associated with decreased endothelial NO release compared with normotensive rats, which is likely owing to a higher production of O 2Ϫ from oxygen in SHR.…”

Section: Discussionmentioning

confidence: 99%

Exaggerated Hypotensive Effect of Vascular Endothelial Growth Factor in Spontaneously Hypertensive Rats

Yang¹,

Ogasawara²,

Zioncheck³

et al. 2002

Hypertension

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Abstract-Vascular endothelial growth factor (VEGF) induces hypotension in normotensive subjects, which is considered to be a major side effect for treatment of ischemic diseases. However, the hypotensive effect of VEGF has not been investigated in the setting of hypertension. This study determined effects of VEGF on hemodynamics, pharmacokinetics, and release of NO and prostaglandin I 2 (PGI 2 ) in vivo and on vasorelaxation of mesentery artery rings in vitro in spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto rats (WKY). Intravenous infusion of VEGF for 2 hours produced a dose-related decrease in arterial pressure, which was enhanced in conscious SHR compared with WKY (PϽ0.01), and an increase in heart rate in WKY but not in SHR. In response to similar doses of VEGF, compared with WKY, SHR had a higher plasma VEGF level and lower VEGF clearance (PϽ0.01). Circulating NO and PGI 2 levels after VEGF administration were not increased in SHR versus WKY, and VEGF-induced vasorelaxation was blunted in SHR versus WKY in vitro, suggesting endothelial dysfunction in SHR. One-week VEGF infusion also caused greater hypotension (PϽ0.05) in the absence of tachycardia in SHR compared with WKY controls. Thus, despite blunted vasorelaxation in vitro because of endothelial dysfunction, SHR exhibited exaggerated hypotension without tachycardia in response to VEGF, which was independent of NO and PGI 2 . The exaggerated hypotensive response to VEGF in SHR may be owing to impaired baroreflex function and reduced VEGF clearance. The data may also suggest that more caution should be taken when VEGF is administered in patients with hypertension. Key Words: growth substances Ⅲ rats, spontaneously hypertensive Ⅲ hemodynamics Ⅲ hypotension Ⅲ blood pressure V ascular endothelial growth factor (VEGF) is a unique mitogen specific for vascular endothelial cells. [1][2][3][4] As a fundamental mediator of normal and pathological angiogenesis, VEGF has been shown to induce a strong angiogenic response in vitro 5,6 and in vivo. 2,3,[7][8][9] Animal studies have demonstrated that administration of VEGF produces beneficial angiogenic effects in peripheral vascular ischemia 10 -12 and in coronary ischemia. [13][14][15][16] VEGF has been shown to induce endothelium-dependent vasorelaxation in normal animals in vitro. [17][18][19] Because of its vasodilatory effect, VEGF induces hypotensive and tachycardic responses in vivo in normotensive animals, including rats, rabbits, and pigs, 14,21 and the hypotensive effect is mediated, at least in part, by NO. 20,21 In humans, intracoronary administration of VEGF caused a hypotensive effect that was dependent on VEGF infusion rate. 22 Although hypotensive effects of VEGF have been characterized in normotensive subjects, these effects have not been investigated in the setting of hypertension.Our previous studies have demonstrated that VEGF induces endothelium-dependent vasorelaxation in aortic rings in vitro, which is diminished in spontaneously hypertensive rats (SHR) compared with normoten...

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Effect of Cilazapril and Indomethacin on Endothelial Dysfunction in the Aortas of Spontaneously Hypertensive Rats

Cited by 26 publications

References 0 publications

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Vasoconstrictor Responses to 5-Hydroxytryptamine in the Autoperfused Hindquarters of Spontaneously Hypertensive Rats

Influence of antihypertensive therapy with cilazapril and hydrochlorothiazide on the stiffness of the aorta

Exaggerated Hypotensive Effect of Vascular Endothelial Growth Factor in Spontaneously Hypertensive Rats

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