Cardiovascular effects of the novel arteriovenous dilator agent, flosequinan in conscious dogs and cats.
1. Flosequinan (BTS 49 465, 7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) a novel arteriovenous dilator agent was orally effective in conscious renal hypertensive dogs and normotensive cats. The hypotensive potency of flosequinan was approximately ten times less than that of hydralazine in renal hypertensive dogs, 10 mg kg-1 and 20 mg kg-1 flosequinan causing similar falls in mean blood pressure to 1 mg kg-1 and 3 mg kg-1 hydralazine respectively. In normotensive cats, 5 mg kg-1 flosequinan caused similar falls to 0.5 and 1.0 mg kg-1 hydralazine. The onset of hypotensive effect after flosequinan appeared to be slightly slower than after hydralazine in the dog and slightly faster than hydralazine in the cat. 2. The degree of tachycardia and increase in plasma renin activity (PRA) for equivalent falls in mean blood pressure in both species was significantly less for flosequinan than for hydralazine (P less than 0.05). 3. In normotensive dogs, flosequinan, 10 and 20 mg kg-1 orally, caused a small but non-significant increase in sodium and chloride excretion and had little effect on urine volume whereas hydralazine, 1 and 3 mg kg-1 orally, caused a marked retention of sodium and chloride ions and a reduction in urine volume (P less than 0.01). 4. Neither flosequinan, 10 mg kg-1 orally, nor hydralazine 1 mg kg-1 orally, affected either glomerular filtration rate measured as creatinine clearance or effective renal plasma flow measured as p-aminohippuric acid clearance in normotensive dogs. 5. The lesser degree of tachycardia and increase in plasma renin activity together with a lack of sodium retaining activity associated with flosequinan suggest that this agent may have potential advantages over existing therapy as an antihypertensive in man.
Sim
M F
MF
Research Department, Boots Co. PLC, Nottingham.
Yates
D B
DB
Parkinson
R
R
Cooling
M J
MJ
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D002712:Chlorides / Q000652:urine; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy; D008297:Male; D011188:Potassium / Q000652:urine; D011804:Quinolines / Q000494:pharmacology*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D014665:Vasodilator Agents / Q000494:pharmacology*
D002712:Chlorides; D011804:Quinolines; D014665:Vasodilator Agents; D006830:Hydralazine; C047316:flosequinan; D012964:Sodium; D012083:Renin; D011188:Potassium