Cardiovascular effects of the calcium-agonistic dihydropyridine BAY K 8644 in conscious dogs.
The hemodynamic effects of the dihydropyridine-derivative BAY K 8644 (methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4-(2-trifluoro-methylphenyl)-pyridine-5-carboxylate), a chemical analogue of Nifedipine, were evaluated in 9 conscious, chronically instrumented dogs. Compared to Nifedipine, BAY K 8644 displays an opposite pharmacological profile. Dose-dependent hemodynamic effects are observed at doses of 4 micrograms/kg i.v. and above. With 32 micrograms/kg i.v. BAY K 8644 increases total peripheral vascular resistance by 100%. It causes a rise of both, systolic and diastolic, blood pressure up to 196/138 mm Hg at spontaneous sinus rhythm and up to 216/162 mm Hg when keeping heart rate constant at 150 beats/minute. Spontaneous heart rate reflexly drops to 52 beats/minute. Cardiac contractility as indicated by LV(dP/dt)max markedly increases from 2800 to 5600 mm Hg/s at spontaneous sinus rhythm and from 2900 to 6100 mm Hg/s while pacing at 150 beats/minute. These effects are apparently neither affected by alpha-adrenergic blockade with Phenoxybenzamine (5 mg/kg i.v.) nor by beta-blockade with Propranolol (0.5 mg/kg i.v.) but can be reserved by equivalent doses of Nifedipine. In conclusion, the Calcium-agonistic dihydropyridine BAY K 8644 due to its novel mechanism of action could be the precursor of a new class of positive inotropic or antihypotensive drugs.
R
R
Gross
M
M
Kayser
M
M
Schramm
R
R
Taniel
G
G
Thomas
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine