Isosorbide 5-mononitrate reverses high blood pressure in NG-nitro-l-arginine methyl ester treated rats

• Type: Article in International Scientific Journal
• Date: 1994

Authors

Albino Teixeira, A (Author) FMUP; soares-da-silva, p (Author) FMUP

Journal

The Journal is awaiting validation by the Administrative Services.

Title: GENERAL PHARMACOLOGY

Vol. 25

Pages: 1329-1336

ISSN: 0306-3623

Indexing

Scopus - 4 Citations

Other information

Authenticus ID: P-007-65B

Abstract (EN): 1. 1. The present study has evaluated the effect of iosorbide 5-mononitrate (IS-5-MN) and l-arginine on blood pressure profile during chronic administration of the nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME). 2. 2. After a 7 day period of stabilization, normotensive male Wistar rats (n = 10) were selected and given L-NAME (50 ¿g/ml) in drinking water. Control rats (n = 10) were studied simultaneously for direct comparison of cardiovascular parameters. Blood pressure (systolic, SBP; diastolic, DBP) and heart rate were measured using a photoelectric tail cuff pulse detector; SBP and DBP were, in normotensive rats 106 ± 2 and 78 ± 2 mmHg (n = 10), respectively. The average water consumption per animal was about 35 ml/day resulting in a mean intake of L-NAME of about 10 mg/kg/day. 3. 3. Twenty four hours after exposure to L-NAME, both SBP and DBP were found to be increased by 20 mm Hg; heart rate slightly decreased. During the next 13 days both SBP and DBP increased progressively reaching 170 ± 3 and 116 ± 3 mm Hg, respectively. 4. 4. On day 14, six animals of either group were sacrificed and the heart, kidneys, liver, spleen, mesenteric and caudal arteries, brain stem, hypothalamus and parietal cortex were taken from determination of noradrenaline and dopamine content; blood from the renal vein was also collected and plasma concentrations of noradrenaline, adrenaline and 3,4-dihydroxyphenylethylglycol (DOPEG) determined. Only in the left atrium of L-NAME-treated rats was noradrenaline found to be increased (9.6 ± 0.5 vs 6.4 ± 0.5 nmol/g; P < 0.02); this effect was accompanied by a significant reduction in dopamine tissue levels (1.4 ± 0.3 vs 0.6 ± 0.1 nmol/g; P < 0.05). Noradrenaline and adrenaline concentrations in plasma were found to be increased in L-NAME-treated rats, whereas DOPEG did not differ significantly between the two groups. 5. 5. Administration of the NO generating compound IS-5-MN (200 ¿g/ml) in drinking water to L-NAME-treated rats resulted in a 25 mm Hg reduction of both SBP and DBP values; this dose of IS-5-MN did not change blood pressure values in control rats. l-Arginine (1.0 mg/ml) in drinking water was found to be unable to reduce SBP and DBP values in L-NAME-treated rats; however, previous administration of l-arginine (1.0 mg/ml) in drinking water completely prevented the hypertensive effect of L-NAME. 6. 6. In conclusion, the present work in normotensive Wistar rats shows that spontaneous oral ingestion of L-NAME causes (at least within 24 hr) hypertension which was sustained for the 21 day observation period and appears to involve chronic NO synthase inhibition. © 1994.

Language: English

Type (Professor's evaluation): Scientific