Enalapril does not prevent the myocardial ischemia caused by the chronic inhibition of nitric oxide synthesis

Moreno, Heitor; Nathan, Luciana Piovesan; Costa, Soraia K.P.; Metze, Konradin; Antunes, Edson; Zatz, Roberto; Nucci, Gilberto De

doi:10.1016/0014-2999(95)00625-x

Cited by 51 publications

(30 citation statements)

References 9 publications

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“…In any case, activation of the renin-angiotensin system is likely to worsen both hypertension and kidney damage, since L-NAME-induced kidney damage can be prevented by angiotensin converting enzyme (ACE) inhibitors (41) and the angiotensin II inhibitor losartan (35). However, myocardial ischemia during L-NAME treatment cannot be prevented by the ACE inhibitor enalapril (42), so other mechanisms must be involved. Increased intake of salt decreased renin release, as expected, which indicates that some control mechanisms were still working in spite of the severe kidney damage.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular Effects of Chronic Inhibition of Nitric Oxide Synthesis and Dietary Salt in Spontaneously Hypertensive Rats.

et al. 1997

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The cardiovascular effects of chronic inhibition of nitric oxide synthesis and dietary salt were studied in 9-wk-old spontaneously hypertensive rats (SHR). Nw-nitro-L-arginine methyl ester (L-NAME, 0.025% in food, about 20 mg/kg/d) was given to rats receiving diets containing low, moderate, and high salt levels (NaC10.2%, 1.1%, and 6.0% of the dry weight of the chow) for 3 wk. L-NAME increased systolic blood pressure by 50 to 60 mmHg in all treated groups, as compared with an average rise of 10 to 20 mmHg in the control SHR. The high-salt diet did not further increase blood pressure. L-NAME also induced cardiac and renal hypertrophy, and these changes were aggravated by the high-salt diet. In addition, 19 of the 30 rats treated with L-NAME suffered strokes and all of them had several myocardial infarctions and renal damage, while the rats not treated with L-NAME had no evidence of stroke or myocardial or renal injury. Responses of mesenteric arterial rings in vitro were studied at the end of the experiment. The vascular contractile responses to noradrenaline were increased, and the relaxation responses to acetylcholine were inhibited in the L-NAME treated groups. In addition, the high-salt diet alone tended to inhibit the response to acetylcholine. Plasma renin activity was markedly increased by L-NAME treatment and decreased by the high-salt diet. The 24-h urine protein excretion was increased both by the L-NAME treatment and by the high-salt diet. The combination of L-NAME and the high-salt diet markedly raised the serum creatinine concentration. Our findings show that the coronary and renal functions are particularly vulnerable in SHR during impaired nitric oxide synthesis, and that the end-organ damage is worsened by an increased intake of dietary salt. We suggest that dysfunction of the endothelium is the primary cause of the effects observed in this study. (Hypertens Res 1997; 20: 183-192)

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Section: Discussionmentioning

confidence: 99%

Cardiovascular Effects of Chronic Inhibition of Nitric Oxide Synthesis and Dietary Salt in Spontaneously Hypertensive Rats.

et al. 1997

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“…Rats receiving chronic L-NAME treatment exhibit focal areas of myocardial necrosis along with focal areas of fibrosis that may reflect organization of necrotic tissue. 98,103 The development of these lesions could not be ascribed to either systemic hypertension 103 or activation of the RAS, 104 suggesting that NO inhibition may exert a specific deleterious effect on the myocardium. Chronic NOS inhibition may also severely damage the CNS.…”

Section: Chronic Nos Inhibition As a Model Of Organ Damagementioning

confidence: 99%

Chronic Nitric Oxide Inhibition Model Six Years On

1998

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Keywords models; cardiovascular diseases; nitric oxide synthase; nitric oxide; blood pressure; reninangiotensin system; vasodilationThe discovery in 1987 that endothelium-derived nitric oxide (NO) mediates the vasodilatory effect of certain endothelium-dependent agonists 1,2 inaugurated the current huge field of NO biology. It is now recognized that NO plays essential roles in many diverse physiological processes and in some pathophysiologic events. Development of these concepts has been based largely on evidence obtained by limiting NO biosynthesis. This review is centered on the cardiovascular and particularly the renal functional and structural consequences of chronic pharmacologic NO inhibition by L-arginine analogues. We devoted special attention to the mechanisms of hypertension and organ injury that occur under these circumstances, while appreciating the inherent limitations surrounding interpretation of this data. Ubiquity and Heterogeneity of NO BiosynthesisNO is made by the enzymatic action of several widely distributed NO synthases (NOS). In the presence of the substrates L-arginine and oxygen, as well as a number of essential cofactors, NO is produced in response to appropriate stimuli. The constitutively expressed NOS play a major role in the physiological control of vascular tone and kidney function. 3,4 Vascular endothelial NOS (eNOS) and brain-type NOS (bNOS) are widely distributed throughout the kidney 5 as well as the cardiovascular system and in strategic locations in the peripheral and central nervous system (CNS). 6,7 Both eNOS and particularly bNOS are abundant in the kidney, glomeruli, and vasculature as well as in most segments of the tubule, 3,5 and NOS activity in medulla is considerably greater than in cortex. 8 NO generated within the kidney controls the glomerular filtration rate (GFR), total renal and medullary blood flow, pressure natriuresis, epithelial sodium transport, and production of various vasoactive factors including renin. 3-5 eNOS is distributed throughout most parts of the arterial and venous circulation, although there is considerable heterogeneity in the extent to which NO controls tone in regional circulations. 9 Although there is some basal NO release from eNOS, shear stress is the physiologically important regulator of vascular NO production. 3 In the CNS, NO is made in the nucleus tractus solitarius, the paraventricular nucleus, and the ventral medulla and can control sympathetic outflow. 6,10 In addition to central regulation of efferent renal sympathetic nerve activity, there is direct nitrergic innervation to several locations including the renal vasculature. 7

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“…Since the reduction of arterial hypertension in this model does not reduce significantly the cardiac and vascular abnormalities, these morbid processes are probably related mainly to NO deficit and not to hypertensive processes (1,(3)(4)(5)(6). Moreno Jr. et al (3,5), using L-Name + enalapril, identified that enalapril avoided arterial hypertension and ventricular hypertrophy; however, did not avoid the development of myocardial lesions. Numaguchi et al (1) showed that on day 56 of concomitant submission to LName and hydralazine, necrotic areas and reparative fibrosis in rats' myocardium occurred.…”

Section: Introductionmentioning

confidence: 99%

“…The L-Name -N ω -nitro-arginine-methyl-ester -is an analog and antagonist of L-Arginine (substract of NO) and via oral or parenteral administration interrupts the NO synthesis which is necessary for maintenance of normal arterial pressure. That causes arterial hypertension, cardiac hypertrophy, vascular abnormalities and lesions in the myocardium (1)(2)(3)(4)(5)(6). Nowadays the degree of direct influence of NO and the influence of its hypertension in the origin of lesions found in heart and vessels is disputed.…”

Section: Introductionmentioning

confidence: 99%

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

Xavier-Vidal¹,

Madi²,

Reis³

et al. 2003

J. Bras. Patol. Med. Lab.

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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

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Enalapril does not prevent the myocardial ischemia caused by the chronic inhibition of nitric oxide synthesis

Cited by 51 publications

References 9 publications

Cardiovascular Effects of Chronic Inhibition of Nitric Oxide Synthesis and Dietary Salt in Spontaneously Hypertensive Rats.

Cardiovascular Effects of Chronic Inhibition of Nitric Oxide Synthesis and Dietary Salt in Spontaneously Hypertensive Rats.

Chronic Nitric Oxide Inhibition Model Six Years On

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

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