The effect of chronic timolol in an animal model for myocardial infarction.
The effect of no drug or timolol (5 mg/kg, PO, for 1, 2, or 8 weeks on postganglionic cardiac sympathetic neural discharge, blood pressure, heart rate and beta-receptor density after acute coronary occlusion of the left anterior descending artery was compared. Beta-receptor density, determined by binding of 3H-dihydroalprenolol, was examined in the myocardium (LA = left atrium, RA = right atrium, LV1 = proximal and LV2 = distal left anterior descending artery distribution, LV3 = posterior left ventricle, S = septum, and RV = right ventricle). In control cats (no coronary occlusion or timolol) beta-receptor density of LV2 and LV3 was greater (P less than .05) than LA, RA, LV1, and RV. LV3 was greater (P less than .05) than S and RA, and LA was less than S. Longer treatment with timolol increased beta-receptor density. When compared with no timolol, beta-receptor density was greater in RA after 8 weeks and in LV1 after 2 weeks and not different in LV2 and S. Beta-receptor density and LV3 and RV were greater after 8 weeks than after 1 week or no timolol. Spearman rank correlation coefficients between dose and beta-receptor density revealed an increase (P less than .05) for all heart areas. Heart rate did not vary before timolol and was decreased after all doses of timolol. Timolol increased the mean times to coronary occlusion-induced death although the increase was not statistically significant. Timolol did not prevent postganglionic cardiac sympathetic neural discharge associated with arrhythmia. Timolol may increase beta-receptor density and decrease synaptic norepinephrine, causing a decreased release per cardiac sympathetic nerve impulse. Alternatively, molecules of timolol may accumulate in nerve endings and be released in greater concentrations at the receptors. This could explain the protection against coronary occlusion-induced arrhythmia and death.
Lathers
C M
CM
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129.
Spivey
W H
WH
Levin
R M
RM
D000758:Anesthesia; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002415:Cats; D004195:Disease Models, Animal; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013999:Timolol / Q000627:therapeutic use*
D011943:Receptors, Adrenergic, beta; D013999:Timolol