Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats.
In order to investigate whether vascular alpha-1 adrenoceptor antagonism plays a role in the antihypertensive effect of verapamil, tiapamil, and nifedipine, we studied their potencies to inhibit K(+)-induced 45Ca2+ influx in rat isolated aorta and [3H]prazosin binding in rat brain membranes in vitro as well as their antihypertensive effect and functional alpha-1 adrenoceptor blockade in conscious spontaneously hypertensive rats (SHR) in vivo. Tiapamil proved 70 times less potent than verapamil in inhibiting calcium influx, but was equipotent in displacing [3H]prazosin. Nifedipine proved 10 times more potent than verapamil as calcium channel blocker but displayed negligible affinity for alpha-1 adrenoceptors in vitro. In conscious SHR, the three calcium channel blockers dose-dependently reduced mean arterial pressure after oral administration. Only at maximal anti-hypertensive doses, the increases in diastolic pressure to intravenous injection of the selective alpha-1 adrenoceptor agonist cirazoline were temporarily suppressed by nifedipine, verapamil, and tiapamil. No relationship existed between the relative potencies as calcium channel blocker and affinities for alpha-1 adrenoceptor binding sites in vitro with functional vascular alpha-1 adrenoceptor blockade in vivo. The data do not support the hypothesis that vascular alpha-1 adrenoceptor blockade plays a significant role in the anti-hypertensive effect of verapamil and related calcium channel blockers.
Thoolen
M J
MJ
E.I. du Pont de Nemours and Company (Inc.), Wilmington, Delaware 19898.
Miller
C R
CR
Chiu
A T
AT
Timmermans
P B
PB
D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002132:Calcium Radioisotopes; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009543:Nifedipine / Q000378:metabolism / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011437:Propylamines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism / Q000502:physiology*; D013268:Stimulation, Chemical; D013976:Tiapamil Hydrochloride; D014316:Tritium; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology*; D014700:Verapamil / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D007093:Imidazoles; D011437:Propylamines; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D014316:Tritium; D014700:Verapamil; D009543:Nifedipine; C014282:cirazoline; D002118:Calcium; D013976:Tiapamil Hydrochloride; D011224:Prazosin