Abstract
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 ± 2%, n = 6) when compared with Sham (80 ± 2%, n = 6, P < 0.05). The maximal response (Emax) to phenylephrine increased in the Inf group (423 ± 10 mm Hg, n = 9, P < 0.01) and decreased in InfHF (279 ± 10 mm Hg, n = 7, P < 0.05) when compared with Sham (319 ± 11 mm Hg, n = 8). Regardless of endothelial integrity, Emax 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 Emax 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.
Footnotes
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doi:10.1124/jpet.104.077701.
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ABBREVIATIONS: MI, myocardial infarction; bw, body weight; RV, right ventricle; LVEDP, left ventricle end diastolic pressure; InfHF, myocardial infarction with heart failure; Inf, myocardial infarction without heart failure; LV, left ventricle; LVSP, left ventricle systolic pressure; +dP/dt, positive rate of pressure development; -dP/dt, negative rate of pressure development; MPP, mean perfusion pressure; ACh, acetylcholine; SNP, sodium nitroprusside; CHAPS, 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid; l-NAME, nitro-l-arginine methyl ester; ANOVA, analysis of variance.
- Received September 11, 2004.
- Accepted November 23, 2004.
- The American Society for Pharmacology and Experimental Therapeutics
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