Effects of the antihypertensive dilevalol on large artery compliance in anesthetized dogs.
The present study examined the actions of dilevalol, an antihypertensive beta-adrenoceptor blocker with arterial vasodilator actions, upon aortic compliance (AC) in anesthetized dogs. AC was determined via sonomicrometric determination of the ratio of aortic systolic-diastolic diameters (mm) and arterial pulse pressure (mm Hg). One AC unit (ACU) equals 10(-3) mm/mm Hg. Dilevalol (0.032, 0.1, and 3.2 mg/kg i.v.) significantly (p less than 0.05) increased AC by 1.4 +/- 0.3, 3.7 +/- 1.4, and 4.5 +/- 1.2 ACU, respectively, from basal values of 4.7 +/- 0.4-5.6 +/- 0.4 ACU, while reducing blood pressure by 20 +/- 2, 31 +/- 9, and 41 +/- 10 mm Hg, respectively (p less than 0.05). Increases in AC were not the passive result of altered blood pressure. Proximal mechanical aortic occlusion dropped systolic blood pressure as much as 70 mm Hg without altering AC. Propranolol (0.32 and 1.0 mg/kg) did not significantly change AC, but propranolol pretreatment attentuated dilevalol-induced increases in AC. Pindolol (0.1-1.0 mg/kg i.v.) lowered blood pressure 17 +/- 3 (p less than 0.05) to 34 +/- 7 mm Hg (p less than 0.05), while significantly increasing AC by 1.2 +/- .2 to 2.7 +/- .7 ACU. The data show that dilevalol, unlike propranolol, increases AC substantially at antihypertensive doses. The inhibition of dilevalol-induced AC increases by propranolol illustrates a beta-adrenoceptor agonist activity in large arteries. Since large artery compliance is impaired in hypertension, dilevalol may afford a vasular protective action for known risk factors for evolving systemic arterial disease.
Watkins
R W
RW
Department of Pharmacology, Schering Corporation, Bloomfield, New Jersey 07003.
Sybertz
E J
EJ
Antonellis
A
A
Pula
K
K
Rivelli
M
M
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure; D003187:Compliance; D004285:Dogs; D005260:Female; D007741:Labetalol / Q000494:pharmacology*; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014463:Ultrasonography
D011433:Propranolol; D010869:Pindolol; D007741:Labetalol