Effect of nitrendipine, nimodipine and nisoldipine on water and electrolytes excretion in rats.

In water loaded (5 ml/100 g) unanesthetized rats. nitrendipine (NT), nimodipine (NM) and nisoldipine (NS) (5 mg/ kg, i.p.) caused significant (P < 0.01) increase in water and Na+ excretion. However, there was no significant increase in K+ excretion after NT, NM and NS administration. NS was more potent in increasing excretion of water load as compared to NT and NM. The glomerular filtration rate as assessed by creatinine clearance, was significantly (P < 0.01) increased in NT, NM and NS (5 mg/kg, i.p.) treated groups as compared to control. The mean creatinine clearance values after NT, NM and NS were 26.95 +/- 0.35, 22.11 +/- 0.72 and 28.13 +/- 0.95 respectively as compared to 22.19 +/- 0.51, 18.77 +/- 0.42 and 22.97 +/- 0.60 in corresponding control groups. The results of the study suggest that in addition to other effects, NT, NM and NS have a selective inhibitory effect on Na+ handling mechanisms in the nephron.

Protection of CCL4-induced liver damage in rats by some calcium channel blockers.

Liver necrosis was produced in rats by administering 3 doses o a mixture o carbon tetrachloide+olive oil, 2 ml/kg, ip. The liver damage was evidenced by the elevated levels serun aspartate aminotrans ferase (AST), alanine aminotransferase (AIT) and gamma glutamyl transpeptidase (gamma-GT) and by histopathological observations of liver sections. Nitrendipine, nimodipine and nisoldipine (1 mg/100 g of rat, ip) significantly reduced these elevated levels of AST, AIT and gamma-GT. Carbon tetrachloride induced liver necrosis was also found to be significantly reduced in nitrendipine, nimodipine and nisoldipine pre-treated animals as observed macroscopically and histologically.

Effect of nitrendipine, nimodipine and nisoldipine on experimentally induced myocardial infarction in rats.

Cardiac necrosis was produced in rats by administering isoproterenol sulphate (85 mg/kg, sc for 4 days). The myocardial damage was proved by observing the elevated levels of serum aspartate aminotransferase, ++alanine aminotransferase and lactate dehydrogenase and the changes were confirmed by his topathology. Nitrendipine, nimodipine and nisoldipine (10 mg/kg, ip) significantly reduced the elevated levels of these enzymes. The average degree of cardiac necrosis in these rats when observed microscopically and histologically was also found to be significantly reduced on pretreatment with these drugs. Nisoldipine was more effective in preventing cardiac necrosis as compared to nitrendipine and nimodipine.

Failure of reversal of cardiovascular responses of clonidine by centrally administered naloxone in anaesthetised rats.

Central effects of naloxone on the cardiovascular responses of centrally administered clonidine were studied in anaesthetised normotensive, renal DOCA-salt hypertensive and morphine dependent rats. Clonidine (5 micrograms/ICV) produced significant decrease in blood pressure and heart rate in all the groups of rats in a dose dependent manner. Naloxone (2 micrograms/ICV) failed to reverse the responses of clonidine in all the rat groups. In morphine dependent normotensive and morphine dependent renal DOCA-salt hypertensive rats, the responses of clonidine were further enhanced in the presence of naloxone. Our observations clearly indicate that clonidine does not influence endogenous opioid system for producing cardiovascular effects.

Comparative evaluation of the vasodilator effect of verapamil, nifedipine and diltiazem on isolated perfused coronary arteries of rabbit.

In experiments with isolated perfused rabbit heart, nifedipine (1, 2 and 4 micrograms) produced a dose-dependent increase in coronary outflow (P less than 0.01). On the other hand effects after verapamil and diltiazem were negligible in such doses, though in high doses (10, 20 and 40 micrograms) they produced a significant (P less than 0.01) increase in coronary outflow. In experiments where noradrenaline (0.1 micrograms/ml) was added in the perfusion fluid, nifedipine (1, 2 and 4 micrograms), as well as verapamil and diltiazem (10, 20 and 40 micrograms) produced a dose-dependent, significant increase in coronary outflow (P less than 0.01).

Effect of glucagon on arrhythmias induced by coronary artery occlusion and ouabain in dogs.

The effect of glucagon in arrhythmias induced by coronary artery occlusion and ouabain was studied in dogs. Intravenous administration of glucagon (50 microgram/kg) to 6 dogs with more than 70% ectopic activity after coronary artery occlusion, resulted in significant (P less than 0.01) decrease in ectopics and increase in heart rate. Infusion of glucagon (2.5 microgram/kg/min) for 30 min caused complete elimination of ectopic activity during infusion period. In another series of 7 experiments, glucagon failed to abolish the ouabain-induced ectopic beats. In fact the hormone itself caused a significant (P less tha 0.01) increase in ectopic activity and heart rate. However, in 7 dogs with complete heart block produced after ouabain conversion to normal sinus rhythm was observed after glucagon.

Effect of glucagon on the perfused rat hind-quarter vessles and on perfused coronary arteries of rabbit.

In rat hind-quarter perfusion experiments, glucagon (1 microgram) produced a significant vasodilation. On the other hand, in experiments with isolated perfused rabbit heart, glucagon (1 microgram) caused coronary vasoconstriction irrespective of whether noradrenaline was added to perfusion fluid or not. Glucagon had no effect on rate or force of contraction of heart.