Effects of Inducible Nitric Oxide Synthase Inhibition on the Rat Tail Vascular Bed Reactivity Three Days After Myocardium Infarction

Abstract

The acute phase of myocardial infarction promotes an inflammatory response that stimulates inducible nitric oxide synthase (iNOS). We investigated the iNOS role on the rat tail vascular bed reactivity 3 days after myocardial infarction. Vasodilator and vasoconstrictor responses were determined in isolated caudal vascular beds from Wistar rats 3 days after coronary artery ligation (CAL) and sham-operated animals (SHAM). Rats were treated with the iNOS inhibitor S-methylisothiourea sulfate (SMT), 5 mg Kg day, i.p. or placebo. Concentration of plasma nitrite/nitrate (NOx) and the expression of iNOS mRNA in tail arteries were evaluated. The CAL group showed increased maximal vasoconstrictor response to phenylephrine (SHAM= 241 +/- 8; CAL= 288 +/- 13 mm Hg, P < 0.05) and SMT treatment normalized this effect (CAL-SMT = 253 +/- 7 mm Hg, P < 0.05). The sensitivity to acetylcholine was reduced in the CAL group, but SMT treatment did not alter this response. The plasma NOx and iNOS mRNA expression in tail arteries were increased in CAL rats. SMT treatment reduced the plasma NOx in the CAL group and the arterial expression of iNOS mRNA in SHAM and CAL group. In conclusion, iNOS inhibition prevented the increased phenylephrine reactivity in rat caudal vascular beds 3 days after myocardial infarction.

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

“…An increase in vascular mRNA for inducible nitric oxide synthase was demonstrated in the acute phase of MI (27). In fact, results from our laboratory have demonstrated that the inducible nitric oxide synthase isoform was not detected in the tail artery of control rats not subjected to surgery (27), but was increased in Sham animals 3 days after surgery (28). Another study demonstrated that prostaglandins, key inflammatory mediators, induce vascular smooth muscle relaxation by stimulating Na + -K + ATPase activity (29).…”

Role of calcium channels responsible for phenylephrine-induced contraction in rat aorta 3 days after acute myocardial infarction

“…A number of studies have demonstrated that NO plays a modulating role in the post-infarction remodeling process, which involves a modest but lasting upregulation of eNOS in blood vessels and cardiomyocytes [2-5]. In contrast, inducible NOS (iNOS) showed dramatic de novo formation 1 week after infarction, predominantly in the infarcted area and cardiomyocytes [5-7]. Moreover, a gradually increased myocardial production of superoxide (O 2 - ) has been detected during remodeling in the peri-infarcted and remote myocardium [5,8,9].…”

“…Some studies have demonstrated that the change of vascular reactivity during the post-infarction remodeling process can occur at non-cardiac vessels such as the large conduit artery or resistant artery [7,10]. However, the effects of vascular contractile responses during the post-infarction remodeling process are determined by the underlying mechanisms.…”

“…However, the effects of vascular contractile responses during the post-infarction remodeling process are determined by the underlying mechanisms. Some reports indicate that the activity of iNOS produces increased α1-adrenergic receptor (AR)-mediated contraction by phenylephrine (PE) in rat caudal vascular beds 3 days after AMI [7]. Other studies suggest that enhanced eNOS activity can play an important role in mediating the reduced vascular growth and decreased PE-induced contractions [10,11].…”

Estudo da função em artérias de resistência de ratos pós-infarto do miocárdio.

“…Por sua vez, existem relatos na literatura de que, enquanto a expressão da iNOS somente é modificada nas artérias em uma fase aguda após o infarto do miocárdio (Bauersachs et al, 1999;Sartório et al, 2005;Berges et al, 2007), a expressão da eNOS, nos vasos arteriais, pode estar reduzida ou até mesmo aumentada (Comini et al, 1996;Smith et al, 1996;Bauersachs et al, 1999;Varin et al, 1999;Gaballa, Goldman, 1999;Berges et al, 2005;Fraccarollo et al, 2008) após o infarto do miocárdio, assim como em outros modelos de cardiomiopatia. Neste sentido, existem relatos de que a expressão protéica da eNOS está reduzida na aorta de cães com insuficiência cardíaca induzida por marcapasso ectópico (Smith et al, 1996), assim como na aorta de ratos com insuficiência cardíaca induzida por monocromalina (Comini et al, 1996).…”