Increased vasoconstrictor activity of proximal coronary arteries with endothelial damage in intact dogs.

Brum, José M.; Sufan, Qian; Lane, Gary E.; Bové, Alfred A.

doi:10.1161/01.cir.70.6.1066

Cited by 109 publications

(25 citation statements)

References 15 publications

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“…1718 Enhanced responses were also noted in the deenddthelialized canine coronary artery. 19 In contrast to previous studies in the WHHL or cholesterol-fed atherosclerotic rabbits, we have shown that alterations in the sensitivity to serotonin precede any evidence of gross atherosclerosis. Enhanced responses were observed in aortas from 1-month-old WHHL rabbits.…”

Section: Discussioncontrasting

confidence: 99%

Augmented vasoconstrictor responses to serotonin precede development of atherosclerosis in aorta of WHHL rabbit.

et al. 1989

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Watanabe heritable hypertlpldemlc (WHHL) rabbits have elevated concentrations of plasma cholesterol and develop progressive atherosclerosis. The present Investigation was undertaken to evaluate the vascular responses to vasoactive compounds of aorta from WHHL rabbits and normal New Zealand White (NZW) rabbits at 1 and 6 months of age. Rings of distal thoracic aorta were suspended under isometric tension in oxygenated Krebs buffer. Developed tension was measured In response to graded concentrations of agonists. Maximal responses to KCI (40 mM) were the same In aortas from the 1-month-old and 6-month-old WHHL and NZW rabbits. Aortas from 1-month-old animals were more sensitive to serotonin than aortas from 6-month-old animals. Aortas from WHHL rabbits exhibited an Increased maximal response to serotonin when compared with NZW controls. In contrast, the constrictor responses to norepinephrine were reduced In WHHL rabbits compared with NZW rabbits at both age groups. Methacholine decreased tension development In serotonin-contracted vessels. This relaxation was greatest In aortas from NZW rabbits. In 1-month-old NZW rabbits fed a high cholesterol diet, the constrictor responses to serotonin and the relaxation responses to methacholine did not differ from NZW rabbits Ingesting a normal diet However, the responses to norepinephrine were markedly attenuated In the hyperchotosterolemlc NZW rabbits. C oronary artery vasospasm has been proposed as one mechanism to account for the episodic reductions in myocardial oxygen delivery in patients with unstable angina pectoris. 1 ' 23 Atherosclerosis may contribute to the development of coronary artery vasospasm through several mechanisms. Atherosclerosis may result in altered responses of the epicardial coronary vessels to vasoactive stimuli by either augmenting responses to vasoconstrictors or diminishing the production of compensatory vasodilatory substances, such as prostacyclin. Also, ath- Received September 24,1987; revision accepted October 24, 1988. erosclerosis may promote the local accumulation of platelets, neutrophils, or macrophages. 45 These cells may release vasoconstrictors that may promote vascular spasm. Other investigators have suggested that hypercholesterotemia per se may augment the reactivity of blood vessels. 6 In the present investigation, we hypothesized that augmented vasoconstrictor responses occur in blood vessels obtained from hypercholesterolemic animals that are prone to devebp atherosclerosis.In these studies, we used the Watanabe heritable hyperiipidemic (WHHL) rabbit. 7 * Homozygous WHHL rabbtts produced by serial inbreeding have plasma cholesterol concentrations of 500 to 950 mg/dl, develop grossly visible aortic atherosclerosis by 5 months of age, 8 -1011 and have decreased numbers of functioning low density lipoprotein (LDL) receptors in several tissues. 812 Thus, this animal model exhibits many clinical and biochemical similarities to familial hypercholesterolemia. To test our hypothesis, we evaluated the vasoconstrictor responses o...

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Section: Discussioncontrasting

confidence: 99%

Augmented vasoconstrictor responses to serotonin precede development of atherosclerosis in aorta of WHHL rabbit.

et al. 1989

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“…The coronary vascular response to 5-HT in the dog varies with vessel size. In this and in earlier studies (Brum et al, 1984;Lamping et al, 1985;Woodman, 1990) 5-HT has been shown to constrict the large coronary arteries but to dilate the resistance vessels. In isolated coronary arteries 5-HT causes the release of endothelium-derived relaxing factor (EDRF, Cocks & Angus, 1983;Cohen et al, 1983) and removal of the endothelium in dogs enhances the constrictor response to 5-HT in the epicardial coronary arteries (Brum et al, 1984;Lamping et al, 1985), suggesting that in large coronary arteries release of endothelium-derived NO normally opposes the direct vasoconstrictor action of 5-HT.…”

Section: Discussionsupporting

confidence: 66%

N‐nitro l‐arginine causes coronary vasoconstriction and inhibits endothelium‐dependent vasodilatation in anaesthetized greyhounds

Woodman

Dusting

1991

British J Pharmacology

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1 The effect of N-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide biosynthesis, on large coronary artery diameter and coronary blood flow was examined in anaesthetized greyhounds. The effects of L-NNA on the coronary vascular responses to acetylcholine (ACh), glyceryl trinitrate (GTN) and 5-hydroxytryptamine (5-HT) were also assessed. 2 L-NNA (5 mg kg 1), infused into the left circumflex coronary artery, increased systemic mean arterial pressure and decreased the external diameter of the artery. Infusion of L-NNA decreased coronary blood flow in 5 of the 7 dogs tested and increased mean coronary resistance but neither of these effects was statistically significant. There was no change in heart rate.3 Intra-arterial injection of both ACh (0.01-0.05#ugkg-1) and GTN (0.1-0.5pgkg-1) increased large coronary artery diameter and coronary blood flow. Coronary vascular responses to the endotheliumdependent vasodilator ACh were significantly reduced by L-NNA, whereas the responses to the endothelium-independent vasodilator GTN were not significantly affected.4 5-HT (0.1lpgkg-1, injected into the left circumflex coronary artery) decreased coronary artery diameter but increased coronary blood flow. After the administration of L-NNA the 5-HT-induced dilatation of the coronary resistance vessels was significantly attenuated whereas the constriction of the circumflex coronary artery was increased in 3 out of 3 dogs in which diameter could be measured, although the latter effect was not statistically significant. 5 These data indicate that L-NNA causes coronary and systemic vasoconstriction and selectively inhibits endothelium-dependent vasodilatation in the coronary circulation of the anaesthetized greyhound. Therefore endothelium-derived NO has an important role in the regulation of coronary vascular tone in the large arteries and the resistance vessels.

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“…The proximal coronary artery constrictor response to 5-hydroxytryptamine was similar to that measured angjographically by Bove and Dewey (1983) in the dog. In a more recent study from the same laboratory, Brum et al (1984) examined the effects of endothelial removal on the constrictor response to 5-hydroxytryptamine. Although disruption of the endothelium appeared to potentiate the constrictor response to 5-hydroxytryptamine, the observed decrease in baseline diameter may have accounted for the reported shift in the dose-response curve.…”

Section: Lamping Et Al /Endothelium and Coronary Artery Constrictionmentioning

confidence: 99%

Removal of the endothelium potentiates canine large coronary artery constrictor responses to 5-hydroxytryptamine in vivo.

Lamping¹,

Marcus²,

Dole³

1985

Circulation Research

119

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SUMMARY. Recent studies in isolated epicardial coronary artery rings have shown that the endothelium modulates vasomotor responses to certain endogenous neurohumoral agents. It is not known whether the endothelium plays a role in large coronary vasoregulation in the intact coronary circulation. Accordingly, we examined effects of endothelial removal on vasoconstrictor responses of the proximal coronary artery in anesthetized adult mongrel dogs. The left anterior descending artery was perfused at 100 mm Hg with arterial blood from a pressurized reservoir. Coronary diameter was measured continuously with 7-MHz sonomicrometer crystals attached to the adventitia of the artery. Fifteen minutes after mechanical disruption of the endothelium with a balloon-tipped catheter, baseline diameter was unchanged from a control value of 2.60 ± 0.13 mm (mean ± SE, n = 17). Endothelial denudation resulted in a dose-dependent potentiation of the constrictor response to intracoronary 5-hydroxytryptamine (1-50 jig/min, n = 8). With the endothelium intact, a 5 /ig/min infusion of 5-hydroxytryptamine reduced diameter by 24 ± 14 /im, while a 50 /ig/min dose reduced diameter by 54 ± 25 fim. After endothelial removal, the decrease in diameter averaged 74 ± 18 ^m at 5 jjg/min and 132 ± 29 /im at 50 jig/min, indicating a 10-fold increase in the sensitivity to 5-hydroxytryptamine. The constrictor responses to angiotensin II (1 and 5 jig/min, n = 7) and phenylephrine (1-5 /ig/min, n = 7) were not altered by endothelial removal. Thus, endothelial removal selectively potentiates the constrictor responses to 5-hydroxytryptamine in the intact coronary circulation of the dog. (Cite Res 57: 46-54, 1985) RECENT studies in isolated arterial preparations including coronary arteries have demonstrated an obligatory role for endothelial cells in the response of vascular smooth muscle to various neurohumoral agents. Removal of the endothelium abolishes vasodilator responses to acetylcholine, bradykinin, thrombin, and substance P (Furchgott and Zawadzki, 1980;Furchgott, 1983) and potentiates vasoconstrictor responses to 5-hydroxytryptamine (Cohen et al., 1983a;Cocks and Angus, 1983).Recently, Cohen and co-workers (1983b) demonstrated that aggregating autologous platelets cause contraction of isolated coronary artery segments. The contractions were augmented after removal of the endothelium, and were attenuated by the 5-hydroxytryptamine antagonists, ketanserin and cyproheptadine. These investigators have also demonstrated that when coronary artery segments are precontracted with prostaglandin F 2a , 5-hydroxytryptamine results in relaxation in some rings with endothelium, but results in contraction in all rings with the endothelium removed. These data suggest that the response of isolated large coronary arteries to 5-hydroxytryptamine is the net result of a direct constrictor effect on the smooth muscle which is opposed by a dilator response mediated by the endothelium (Cohen et al., 1983a). These in vitro observations have suggested that the absence o...

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Increased vasoconstrictor activity of proximal coronary arteries with endothelial damage in intact dogs.

Abstract: In this study we

Cited by 109 publications

References 15 publications

Augmented vasoconstrictor responses to serotonin precede development of atherosclerosis in aorta of WHHL rabbit.

Augmented vasoconstrictor responses to serotonin precede development of atherosclerosis in aorta of WHHL rabbit.

N‐nitro l‐arginine causes coronary vasoconstriction and inhibits endothelium‐dependent vasodilatation in anaesthetized greyhounds

Removal of the endothelium potentiates canine large coronary artery constrictor responses to 5-hydroxytryptamine in vivo.

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