Reduced responsiveness of rat mesenteric resistance artery smooth muscle to phenylephrine and calcium following myocardial infarction

Stassen, Frank R. M.; Willemsen, Mark G. A.; Janssen, G. M. E.; Fazzi, Gregorio E.; Schiffers, P. M. H.; Smits, J. F. M.; Mey, Jo G. R. De

doi:10.1038/sj.bjp.0701089

Cited by 22 publications

(14 citation statements)

References 42 publications

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“…Although we did not evaluate the neurohumoral activation, the InfHF rats presented hyporeactivity to the ␣-agonist phenylephrine. In contrast with a down-regulation of ␣-adrenoceptors found in rat mesenteric arteries after MI, Feng et al (1996) and Stassen et al (1997b) found no changes in the density of ␣ 1 -adrenoceptors in those vascular beds that displayed a decreased responsiveness to phenylephrine. However, absence of changes in the density of ␣ 1 -adrenoceptors does not rule out changes in the receptor signaling pathway that may lead to a reduction in responsiveness.…”

Section: Discussionmentioning

confidence: 55%

Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction

Pereira¹,

Sartório²,

Vassallo³

et al. 2004

J Pharmacol Exp Ther

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Myocardial infarction (MI) was induced in rats by coronary ligation to compare changes in vascular reactivity from animals that developed heart failure (InfHF) with those that did not (Inf). Infarct size was similar in both groups. In vitro preparations of tail vascular bed were used to investigate the vascular responses to acetylcholine, sodium nitroprusside, and phenylephrine. Acetylcholine-induced relaxation was impaired in the Inf group (53 Ϯ 2%, n ϭ 6) when compared with Sham (80 Ϯ 2%, n ϭ 6, P Ͻ 0.05). The maximal response (E max ) to phenylephrine increased in the Inf group (423 Ϯ 10 mm Hg, n ϭ 9, P Ͻ 0.01) and decreased in InfHF (279 Ϯ 10 mm Hg, n ϭ 7, P Ͻ 0.05) when compared with Sham (319 Ϯ 11 mm Hg, n ϭ 8). Regardless of endothelial integrity, E max to phenylephrine increased in the Inf, nitro-L-arginine methyl ester, and indomethacin groups. An increased release of a prostanoid vasodilator was detected in the Inf group. Differently, the InfHF group presented a reduction of the E max to phenylephrine and an increment of nitric oxide release. This study demonstrates that MI without heart failure impairs endothelium-dependent relaxation and increases the reactivity to phenylephrine. This increase seems to involve a muscular component. The endothelium participates with an increased release of a vasodilator prostanoid, possibly to compensate the increased smooth muscle response. When heart failure follows MI, the reactivity to phenylephrine decreases, possibly due to an increased nitric oxide release.Coronary artery ligation in rats has been used as a model of chronic left ventricular failure that closely mimics human condition (Hodsman et al., 1988). Indeed, compromised cardiac function (De Felice et al., 1989;Solomon et al., 1999) and increased peripheral resistance (Drexler and Lu, 1992;Schrier and Abraham, 1999) are found in this model. Systemic vasoconstriction can result from many compensatory mechanisms, including activation of the renin-angiotensin system, activation of the sympathetic nervous system, and alterations in the synthesis of local vascular factors (Zelis and Flaim, 1982;Gschwend et al., 2003).Much has been reported regarding endothelial dysfunction in postinfarction myocardial failure (Teerlink et al., 1993(Teerlink et al., , 1994Didion et al., 1997;Bauersachs et al., 1999;Indik et al., 2001;Gschwend et al., 2003), but there is no consensus regarding vascular function in heart failure due to heterogeneity of alterations in vascular reactivity. These alterations may depend on the duration of the disease and the type of artery studied (Stassen et al., 1997a). Despite much research on vascular reactivity in postinfarction heart failure, little is known concerning vascular reactivity in a chronic phase of myocardial infarction (MI), when heart failure is absent.The purpose of this study was, in the first place, to show that there are two animal models with similar infarction areas produced by coronary ligation: chronic MI without heart failure and with heart failure and, secondly, ...

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Section: Discussionmentioning

confidence: 55%

Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction

Pereira¹,

Sartório²,

Vassallo³

et al. 2004

J Pharmacol Exp Ther

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“…Arteries of increasing branching order were made to contract with phenylephrine. This agonist activates α 1 ‐adrenoceptors that are expressed by ASM cells (Stassen et al. , 1997) but do not directly stimulate calcium influx in endothelial cells (Dora et al.…”

Section: Discussionmentioning

confidence: 99%

“…Arteries of increasing branching order were made to contract with phenylephrine. This agonist activates a1-adrenoceptors that are expressed by ASM cells (Stassen et al, 1997) but do not directly stimulate calcium influx in endothelial cells (Dora et al, 2000). Because it can be debated whether the endothelium of small arteries and arterioles expresses a1-adrenoceptors (Tuttle and Falcone, 2001), additional smooth muscle stimuli were also used.…”

Section: Rhp Hilgers and Jgr De Meymentioning

confidence: 99%

Myoendothelial coupling in the mesenteric arterial bed; segmental differences and interplay between nitric oxide and endothelin‐1

Hilgers

Mey

2009

British J Pharmacology

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Background and purpose: We tested the hypothesis that activated arterial smooth muscle (ASM) stimulates endothelial vasomotor influences via gap junctions and that the significance of this myoendothelial coupling increases with decreasing arterial diameter. Experimental approach: From WKY rats, first-, second-, third-and fourth-order branches of the superior mesenteric artery (MA1, MA2, MA3 and MA4 respectively) were isolated and mounted in wire-myographs to record vasomotor responses to 0.16-20 mmol·L -1 phenylephrine. Key results: Removal of endothelium increased the sensitivity (pEC50) to phenylephrine in all arteries. The nitric oxide (NO) synthase inhibitor N w -nitro-L-arginine methyl ester (L-NAME) (100 mmol·L -1 ) did not modify pEC50 to phenylephrine in all denuded arteries, and increased it in intact MA1, MA2 and MA3 to the same extent as denudation. However, in intact MA4, the effect of L-NAME was significantly larger (DpEC50 0.57 Ϯ 0.02) than the effect of endothelium removal (DpEC50 0.20 Ϯ 0.06). This endothelium-dependent effect of L-NAME in MA4 was inhibited by (i) steroidal and peptidergic uncouplers of gap junctions; (ii) a low concentration of the NO donor sodium nitroprusside; and (iii) by the endothelin-receptor antagonist bosentan. It was also observed during contractions induced by (i) calcium channel activation (BayK 8644, 0.001-1 mmol·L

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“…NE content of the extract was measured by high-performance liquid chromatography and fluorescent detection, 19 after which the tissues were solubilized in 1N KOH (24 hours, room temperature) and DNA content was determined. 20 Unlike for NE, the levels of dopamine and epinephrine were below detection limits in the embryonic arteries and heart.…”

Section: Ne and Dna Contentmentioning

confidence: 99%

Chronic Hypoxia Stimulates Periarterial Sympathetic Nerve Development in Chicken Embryo

et al. 2000

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Background-Epidemiological findings suggest an association between low-for-age birth weight and the risk to develop coronary heart diseases in adulthood. During pregnancy, an imbalance between fetal demands and supply may result in permanent alterations of neuroendocrine development in the fetus. We evaluated whether chronic prenatal hypoxia increases arterial sympathetic innervation. Methods and Results-Chicken embryos were maintained from 0.3 to 0.9 of the 21-day incubation period under normoxic (21% O 2 ) or hypoxic conditions (15% O 2 ). At 0.9 incubation, the degree of sympathetic innervation of the embryonic femoral artery was determined by biochemical, histological, and functional (in vitro contractile reactivity) techniques. Chronic hypoxia increased embryonic mortality (32% versus 13%), reduced body weight (21.9Ϯ0.4 versus 25.4Ϯ0.6 g), increased femoral artery norepinephrine (NE) content (78.4Ϯ9.4 versus 57.5Ϯ5.0 pg/mm vessel length), and increased the density of periarterial sympathetic nerve fibers (14.4Ϯ0.7 versus 12.5Ϯ0.6 counts/10 4 m 2 ). Arteries from hypoxic embryos were less sensitive to NE (pD 2 , 5.99Ϯ0.04 versus 6.21Ϯ0.10). In the presence of cocaine, however, differences in sensitivity were no longer present. In the embryonic heart, NE content (156.9Ϯ11.0 versus 108.1Ϯ14.7 pg/mg wet wt) was also increased after chronic hypoxia. Conclusions-In the chicken embryo, chronic moderate hypoxia leads to sympathetic hyperinnervation of the arterial system. In humans, an analogous mechanism may increase the risk for cardiovascular disease in adult life. (Circulation.

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Reduced responsiveness of rat mesenteric resistance artery smooth muscle to phenylephrine and calcium following myocardial infarction

Cited by 22 publications

References 42 publications

Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction

Differences in Tail Vascular Bed Reactivity in Rats with and without Heart Failure following Myocardial Infarction

Myoendothelial coupling in the mesenteric arterial bed; segmental differences and interplay between nitric oxide and endothelin‐1

Chronic Hypoxia Stimulates Periarterial Sympathetic Nerve Development in Chicken Embryo

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