Hydralazine reduces myocardial tissue damage in rats submitted to chronic inhibition of systemic nitric oxide synthesis during 4, 14 and 28 days

Abstract

y key words unitermos abstractThe aim of the present work was to develop a qualitative chronopathological study concerning abnormalities in myocardium, due to nitric oxide (NO) blockage. We used 60 Wistar normotensive young male rats from several breeds. Groups of rats were submitted to L-Name (L) via oral administration dissolved in water (750mg/l) during days 4, 14 and 28. Other groups were submitted concomitantly to L-Name and hydralazine hydrocloride (L + H) (120mg/l). On days 4 and 14 (L group) we have found myocardial abnormalities and lesions while in L + H we could not identify abnormalities. Considering L group on day 28, the myocardium presented characteristic fibrosis (reactive and reparative), vascular damage with increasing wall thickness due mainly to proliferation of the arterial smooth muscle cell. Total obliteration of vessels was noted only in this period. We also observed reactive fibrosis between muscle cells of the vascular wall and proliferation of cells in the intimal layer. In L + H (day 28), similar vascular abnormalities described for L group (less frequent and less apparent) were also observed. In L + H we did not identify total vascular obstructions. In L + H, infarct areas were not observed. Control groups did not present any abnormalities. Our results support the idea that, at least in some cases, hypertrophy vascular abnormalities and myocardial lesions in arterial hypertension can occur because of the reduction in organic nitric oxide production. Our results also suggested that these morbid processes can be postponed by the use of hydralazine which, however, does not avoid abnormalities after long-term experimental blockage of NO. O alvo do presente trabalho foi desenvolver um estudo cronopatológico experimental referente a anormalidades miocárdicas com origem no bloqueio sistêmico da síntese do óxido nítrico. Utilizamos 60 ratos wistar machos jovens, oriundos de várias ninhadas. Grupos de ratos foram submetidos ao L-Name (L), por administração via oral, dissolvido em água (750mg/l), durante quatro, 14 e 28 dias. Outros grupos foram submetidos concomitantemente ao L-Name e ao hidrocloreto de hidralazina (L + H) (120mg/l). Aos quatro e 14 dias (grupo L) encontramos anormalidades miocárdicas e lesões. Contudo, nos grupos L + H, aos quatro

Inhibition of nitric oxide synthesis for four days induces vascular abnormalities and myocardial infarct areas but not significant arterial hypertension

“…In the present work, using NO systemic blockage (L-NAME Model), we identified increase of vascular media, fibrotic scars, and perivascular fibrosis in left, right, and septal myocardium, similar to those lesions found by Hocher 26 in renovascular hypertension. Felix et al 16 , using infusion dose of aldosterone and angiotensin II in rats, found reactive and reparative fibrosis similar to those found in previous [5][6][7][8][9]18,19,22 and present works.…”

“…Nowadays, it has been discussed the degree of direct influence of NO -and the influence of hypertension produced by NO blockagein hypertrophy and cardiac lesions in the L-NAME model. Since the reduction of arterial hypertension in this model does not reduce significantly the hypertrophy and the lesions, these morbid processes are probably related to NO deficit 6 . Some studies showed that at least in some cases of hypertension, NO synthesis is reduced [10][11][12] .…”

“…Also, the basal arterial pressure reduces about 20 mmHg in mice with eNOS overexpression 23 . NO blockage has been suggested as promoting fibrosis [5][6]8,[18][19]25 . Hocher 26 , working with renovascular hypertension (Goldblatt's method, left renal artery), found abnormalities in media/lumen ratio in intramyocardial vessels.…”

“…After the evaluation of the arterial pressure, each rat was placed in an individual plastic box. To perform NO blockage, we utilized L-NAME (Sigma Chemical, St. Louis) via oral administration at concentration of 75 mg/100 mL in drinking water (about 60 milligrams per kilograms of body weight) [5][6][7][8][9][18][19][20][21][22] . We submitted eight rats during four days to L-NAME (Group L) and six were utilized as a Control Group (Group C).…”

“…Nitric oxide (NO) is a vascular smooth muscle relaxation factor. The L-NAME, N ω -nitro-arginine-methyl-ester, is an analog and antagonist of L-arginine (Substract of NO Synthase, NOS) and its oral or parentheral administration interrupt the NO synthesis, which is necessary for the maintenance of normal arterial pressure that causes arterial hypertension, a significant experimental cardiac hypertrophy, and lesions on myocardial mass [1][2][3][4][5][6][7][8][9] . Nowadays, it has been discussed the degree of direct influence of NO -and the influence of hypertension produced by NO blockagein hypertrophy and cardiac lesions in the L-NAME model.…”