Impaired vascular smooth muscle nitric oxide-dependent relaxation in human coronary arteries from "transplanted heart vasculopathy".

The long-term prognosis after heart transplant is mainly determined by the development of transplant vasculopathy. The pathogenic mechanism of transplant vasculopathy remain uncertain, although endothelial dysfunction has been postulated. The objective of this work is to evaluate the smooth muscle and endothelium nitric oxide relaxing mechanisms in coronary arteries from patients with transplant vasculopathy. We studied human coronary arteries obtained from heart transplant surgery specimens of patients with heart transplant vasculopathy, ischaemic cardiopathy or dilated cardiomyopathy. Rings from the coronary arteries were mounted on stainless steel hooks in 40 ml organ bath. The tissues were contracted with phenylephrine (approx. ED 80-90) and concentration-response curves were performed with glyceryltrinitrate and acetylcholine. Glyceryltrinitrate relaxed arterial rings from patients with dilated cardiomyopathy and ischaemic cardiopathy. Arterial rings from patients with heart transplant vasculopathy showed a lower response to glyceryltrinitrate. Acetylcholine induced dilatation of coronary arteries from dilated cardiomyopathy but increased the tension in coronary rings from heart transplant vasculopathy and inschaemic cardiopathy. In conclusion, there is a lower response to glyceryltrinitrate and a paradoxical response to acetylcholine in arteries from patients with transplant vasculopathy. The response to glyceryltrinitrate may be a meaningful tool in the early diagnosis of transplant vasculopathy.

Local transdermal glyceryl trinitrate has an antiinflammatory action on thrombophlebitis induced by sclerosis of leg varicose veins.

To test the antiinflammatory and analgesic effects of transdermal glyceryl trinitrate (GTN) the authors carried out a double-blind, randomized, controlled clinical study in 21 patients with mild to moderate leg varicose veins who underwent vein sclerotherapy in both legs. GTN or placebo ointment was applied in a blinded protocol along the surface of the sclerosed vein every eight hours until disappearance of inflammation signs. The varicose vein in one leg was treated with GTN and compared with placebo for the vein of the other leg used as control of thrombophlebitis (TP) signs. Fifteen minutes after first application inflammation signs were observed in all cases. The intensity of inflammation signs was assessed as 26% (10.4 +/- 4.1) in GTN-treated veins and as 61.5% (24.6 +/- 6.3) (P < 0.001) in the placebo-treated veins. One hour later only 63% of cases in the GTN group and all cases in the placebo group showed signs of TP (P < 0.001). The reduction in the intensity of signs at this time was 7.7 +/- 3.9 in the GTN group and 19.7 +/- 6.3 in the placebo group (P < 0.001). All veins in the GTN group were free of signs of TP in less than forty-eight hours. In the placebo group, 45% of veins required more than forty-eight hours for complete disappearance of signs of TP (P < 0.001). The authors conclude that GTN has an antiinflammatory effect in TP induced by sclerotherapy. This action may be related to the nitric oxide released from GTN, through a direct action on the vein and the surrounding inflamed tissue.

Induction of nitric oxide synthase in human mammary arteries in vitro.

This study investigated whether human mammary arteries express an inducible nitric oxide (NO) synthase and, if so, what its effects are on vascular tone. In human mammary artery pre-contracted with phenylephrine there was a gradual time-dependent loss of tone over an 8 h period. L-Arginine and lipopolysaccharide enhanced the rate but not the magnitude of this loss in tone, whereas NG-nitro-L-arginine, NG-monomethyl-L-arginine, dexamethasone, and polymyxin B inhibited these effects. These findings indicate that incubation of human mammary artery with lipopolysaccharide resulted in the expression of an inducible NO synthase. The induction of this enzyme in human vessels may be important in the pathogenesis of septic shock.

[The peripheral analgesic action of the exogenous nitric oxide donor: nitroglycerin. A placebo-controlled study of the transdermal action of nitroglycerin on pain sensitivity in the forearm]. / Acción analgésica periférica del donador exógeno de óxido nítrico: nitroglicerina. Estudio control frente a placebo de la acción de la nitroglicerina transdérmica sobre la sensibilidad dolorosa en el antebrazo.

Nitric oxide is a biological mediator. In nervous system it acts like neurotransmitter and also modulate acute inflammation. In the peripheral nervous system it blocks the nociceptive stimulus through an increase in postsynaptic neurone GMPc level. Nitro-vasodilator drugs like nitroglycerin are metabolised in the cell given rise to short lived intermediates, which liberating nitric oxide that activate the guanylate cyclase enzyme, increasing the GMPc in smooth muscle cell. This study show that nitroglycerin produces an analgesic action. The pain sensitivity to pinprick test in forearm with nitroglycerin has shown a decrease in a significative manner against placebo. We speculate that nitroglycerin could have a similar action as endogenous nitric oxide in nervous system.

Spectrum of heart malformations in mice with situs solitus, situs inversus, and associated visceral heterotaxy.

BACKGROUND: We present a study of the heart malformations found in a collection of mouse fetuses of the iv/iv strain between days 16.5 and 18.5 of gestation. METHODS AND RESULTS: One hundred hearts were serially sectioned and studied by segmental analysis with a light microscope. Forty additional hearts were analyzed with a scanning microscope. Forty percent of the hearts were found to be malformed. The most frequently occurring heart malformations were persistence of the sinus venosus (9%), common atrium (17%), common atrioventricular canal (24%), double-outlet right ventricle (12%), Fallot's tetralogy (8%), and transposition of the great arteries (5%). These malformations do not usually occur in isolation but rather appear in the formation of complex cardiopathies. The most severe and frequent is the combination of persistence of sinus venosus, common atrium, common atrioventricular canal, and double-outlet right ventricle; this is the "bulboventricular heart." The morphology of each lesion, as well as the degree of association, is similar to that found in human hearts with complex cardiopathies. Some of these cardiopathies appear to be directly related to formation of the cardiac loop. The iv/iv mouse appears to constitute an excellent model with which to study the etiology and pathogenesis of complex heart defects in humans. These hearts show a high phenotypic variability in the presentation of heart lesions. From a genetic viewpoint, there is a basic defect--the bulboventricular heart--which can be considered congenital. The other malformations can be considered formes frustes of the defect type. CONCLUSIONS: The iv gene is a developmental gene that affects basic developmental mechanisms. In this regard, heart lesions may not be the primary result of the abnormal gene activity but rather are secondary to defective interactions during cardiac development.