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Effect of Ca2+ channel blockers on arterial hypertension and heart ischaemic lesions induced by chronic blockade of nitric oxide in the rat.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1999 Jun 04; Vol. 373 (2-3), pp. 195-200. - Publication Year :
- 1999
-
Abstract
- The effects of the Ca2+ channel blockers diltiazem, nifedipine and amlodipine were investigated on both arterial hypertension and myocardial changes induced by chronic blockade of nitric oxide synthesis. Control male Wistar rats received Nomega-nitro-L-arginine methyl ester (L-NAME; 20 mg rat(-1) day(-1)) in the drinking water for 8 weeks; blood pressure and body weight were monitored weekly. The Ca2+ channel blockers were given concomitantly to L-NAME, as follows: diltiazem (13.5 mg rat(-1) day(-1)) and amlodipine (6.25 mg rat(-1) day(-1)) were administered in the drinking water whereas nifedipine (6.25 mg rat(-1) day(-1)) was given in the chow. Nomega-nitro-L-arginine methyl ester induced a time-dependent increase in blood pressure which was significantly attenuated by diltiazem (154+/-1.6 vs. 139+/-1.6 mm Hg, p < 0.05), nifedipine (166+/-2.7 vs. 150+/-2.1 mm Hg, p < 0.05) and amlodipine (208+/-5.8 vs. 158+/-1.8 mm Hg, p < 0.05) at the last week of the treatment. Rats treated with the L-NAME also developed myocardial ischaemia, as indicated by the increased percentage of fibrous tissue found in the left ventricles of these animals (10.9+/-0.1%, p < 0.01) when compared to control ones (6.3+/-0.1%). Neither diltiazem (14.9+/-1.2%) nor nifedipine (11.1+/-1.5%) prevented this effect whereas amlodipine (6.9+/-1.1%, p < 0.01) virtually abolished the increase in fibrous tissue induced by L-NAME. The plasma concentration of the Ca2+ channel blockers was measured by liquid chromatography coupled to mass spectrometry at two different time points (morning and afternoon). Only amlodipine treatment was able to maintain constant levels (186+/-46 ng ml(-1) in the morning and 110+/-19 ng ml(-1) in the evening) compared to nifedipine (3003+/-578 ng ml(-1) in the morning and 436+/-100 ng ml(-1) in the evening) and diltiazem (77+/-51 ng ml(-1) in the morning and not detectable in the evening). In conclusion, our results indicate that amlodipine (but not diltiazem and nifedipine) can efficiently control myocardial ischaemia in nitric oxide deficient rats, probably due to its intrinsically long half-life.
- Subjects :
- Animals
Blood Pressure drug effects
Blood Pressure Determination methods
Body Weight drug effects
Calcium Channel Blockers blood
Diltiazem blood
Diltiazem pharmacology
Enzyme Inhibitors pharmacology
Heart Ventricles drug effects
Heart Ventricles pathology
Hypertension metabolism
Hypertension physiopathology
Male
Myocardial Ischemia metabolism
Myocardial Ischemia physiopathology
NG-Nitroarginine Methyl Ester pharmacology
Nifedipine blood
Nifedipine pharmacology
Rats
Rats, Wistar
Survival Analysis
Calcium Channel Blockers pharmacology
Hypertension prevention & control
Myocardial Ischemia prevention & control
Nitric Oxide metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 373
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10414439
- Full Text :
- https://doi.org/10.1016/s0014-2999(99)00267-8