Structural changes in the myocardium following inhibition of nitric oxide synthesis were studied quantitatively within two different periods. Four groups of 10 rats were studied: control and L-NAME (NG-nitro-methyl-ester-L-arginine) groups for 25 and for 40 days. L-NAME was administered at 50 mg/kg per day in the drinking water. On the 26th and 41st days, the hearts were examined. Volume densities of myocytes (Vv[m]), cardiac interstitium (Vv[int], numerical density of myocytes (Nv[m]) and mean cross-sectional area of the myocytes (A[m]) were determined. Comparing the L-NAME animals with their respective controls showed the arterial pressure (AP) and the heart weight (HW) to be increased in the L-NAME animals. At 25 days, and more obviously at 40 days, the myocytes were hypertrophied with increase of myofibrils (A[m], greater in L-NAME rats). There were some areas with ischaemic lesions, inflammatory infiltrates and perivascular and interstitial fibrosis. The intramyocardial arteries had a thick tunica media and tunica intima. At 25 days the myocardium showed no stereological difference between L-NAME and controls, but by 40 days there was decreased Vv[m] and Nv[m] and increased Vv[int] in the exposed group. Inhibition of NO synthesis provoked a time progressive myocardial change, quantified by stereology.

Objective: The myocardial effect on the normalization of arterial blood pressure in animals with hypertension previously induced by nitric oxide synthesis (NOS) inhibition is still unknown. The purpose of this study was to estimate the numerical density of cardiomyocytes that is able to show cardiomyocyte loss as a consequence of NOS inhibition. Methods: Sixty rats were divided into the following groups: control for 25 days (C25), control for 40 days (C40) control for 80 days (C80) and three other groups in which the rats received the NOS inhibitor N(G)-nitro-L-arginine-methyl-ester hydrochloride L-NAME; 50 mg/kg/day for 25 days (L25), 40 days (L40) and 40 days, respectively, the latter group having another 40 days of only water and food ad libitum (without L-NAME; L80 group). The detection of apoptotic cells was performed using a monoclonal antibody. Results: In the L25, L40 and L80 groups, blood pressure was 74.5, 90.2 and 56.3% higher than the respective age-matched control rats, the myocardium had hypertrophy of the cardiomyocytes and scattered areas of fibrosis, and apoptosis occurred in isolated cells. Compared to the controls, the heart mass/body mass ratio was significantly greater in the L-NAME groups L25, L40 and L80, i.e. 31, 26 and 21%, respectively, the numerical density of cardiomyocytes in L-NAME rats was 32.7, 48.8 and 41.7% lower and the mean volume of cardiomyocytes was 33, 53 and 48% greater. Conclusion: The cardiomyocyte loss in NOS inhibition seems to be mainly due to necrosis, although apoptosis is also present.

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The nitric oxide (NO) is a small hydrophobic gas molecule synthesized from L-arginine by a process that can be competitively inhibited by L-arginine analogues, such as L-NAME [1]. The NO synthesis (NOs) has a major physiological regulator function on vascular resistance and renal hemodynamics, as well as on proximal tubular reabsorption activity [2].The chronic NOs blockade has a great impact on renal hemodynamics, causing marked vasoconstriction, reduction of glomerular filtration rate, and proteinuria [3][4]. In this case the renal blood flow decreased, approximately 25%, reducing sodium excretion without reductions in filtered load, suppressing the slope of the arterial pressuremediated response in sodium excretion [5][6]. The J. Cell.Mol.Med. Vol 5, No 3, 2001 pp. 276-283 Renal cortical remodelling by NO-synthesis blockers in rats is prevented by angiotensin-converting enzyme inhibitor and calcium channel blocker AbstractThe cortical remodelling was studied when chronically nitric oxide synthesis (NOs) blockade (L-NAME-induced) hypertensive rats are simultaneously treated, or not, with angiotensin-converting enzyme inhibitor or calcium channel blocker. Four groups of eight rats each were studied as follows: Control (C), L-NAME (L), LNAME+Enalapril (L+E) and L-NAME+Verapamil (L+V). The systolic blood pressure (SBP) was weekly recorded. The cortex of the left kidneys was analysed according to the vertical section design. The volume-weighted mean glomerular volume (VWGV) was made through the "point-sampled intercepts" method. Enalapril and verapamil were efficient in reducing the SBP in rats submitted to NOs blockade. Glomeruli had considerable alterations in L group rats (glomerular hypertrophy or sclerosis) and tubular atrophy. The VWGV was 100% greater in L group rats than in the C group rats, while it was 30% smaller in L+E and L+V groups than in L group. The tubular volume was 30-50% greater, while the tubular length was 20-30% smaller in the L group than in the other groups. The renal cortical region showed glomerular sclerosis/hypertrophy and tubular remodelling in rats with NOs blockade that was efficiently prevented with the simultaneous treatment with enalapril or verapamil.

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