Vasorelaxant and Hypotensive Effects of Tilisolol Hydrochloride (N-696) in Isolated Rat Thoracic Aorta and Pithed Rats

• Published in: Japanese Journal of Pharmacology Vol. 57; no. 3; pp. 367 - 375
• Main Authors: Sugai, Toshiji, Kojima, Kazuko, Iwakami, Naomi, Suzuki, Yoshikuni
• Format: Journal Article
• Language: English; Japanese
• Published: Kyoto The Japanese Pharmacological Society 1991; Japanese Pharmacological Society
• Subjects: Adrenergic beta-Antagonists - pharmacology; Animals; Antihypertensive agents; Aorta, Thoracic - drug effects; Benzopyrans - pharmacology; Biological and medical sciences; blood pressure; Blood Pressure - drug effects; Cardiovascular system; Cromakalim; Dose-Response Relationship, Drug; Glyburide - pharmacology; Hypotension - chemically induced; In Vitro Techniques; induction; Isoquinolines - antagonists & inhibitors; Isoquinolines - pharmacology; Male; Medical sciences; Pharmacology. Drug treatments; Pyrroles - pharmacology; Rats; Rats, Inbred Strains; reduction; tilisolol hydrochloride; Vasodilator Agents - antagonists & inhibitors; Vasodilator Agents - pharmacology; vasorelaxation; Vasodilator agent; Rat; Spinal animal; Rodentia; Smooth muscle; Muscle contraction; In vitro; Biological activity; Thoracic aorta; Vertebrata; Mammalia; Antihypertensive agent; Beta blocking agent
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.57.367

Vasorelaxant and hypotensive effects of tilisolol hydrochloride (N-696) in isolated rat thoracic aorta and pithed rats were investigated. In rat thoracic aorta pre-contracted with KCl (20 mM), tilisolol (10-5-10-3 M) produced concentration-related relaxation, but nadolol and atenolol did not significantly inhibit the responses to 20 mM KCl. The concentration-relaxation curve of tilisolol underwent rightward parallel shifts only to a limited extent in the presence of glibenclamide, a specific antagonist of K+ channel openers. Glibenclamide also shifted the concentration-relaxation curve of cromakalim to the right and in a parallel manner, whereas it did not change that of propranolol. In pithed rats, tilisolol (0.5-2.0 mg/kg, i.v.), but neither nadolol nor atenolol, caused a dose-dependent decrease in diastolic blood pressure and a slight increase in heart rate. Following treatment of the preparation with glibenclamide, the hypotensive effects of tilisolol and cromakalim were antagonized, while that of propranolol was not affected. These results suggest that the vasorelaxant and hypotensive actions of tilisolol involve an opening of K+ channels which can be inhibited by glibenclamide and may also involve additional relaxant mechanisms of action independent of K+ channel opening.