Effect of calcium entry blockers on blood pressure and vasoconstrictor responses to alpha-1 adrenoceptor stimulation in conscious spontaneously hypertensive rats

Journal Article · Tue Dec 01 04:00:00 EST 1987 · Cardiovascular Drugs and Therapy; (USA)

DOI:https://doi.org/10.1007/BF02209079· OSTI ID:5574616

Thoolen, M J; Miller, C R; Chiu, A T; Timmermans, P B ^[1]

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1. E.I. du Pont de Nemours and Company Inc., Wilmington, DE (USA)

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 ({sup 3}H)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 ({sup 3}H)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.

• OSTI ID: 5574616
• Journal Information: Cardiovascular Drugs and Therapy; (USA), Journal Name: Cardiovascular Drugs and Therapy; (USA) Vol. 1:4; ISSN CDTHE; ISSN 0920-3206
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ALKALINE EARTH METALS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZOLES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BLOOD PRESSURE
BODY
BRAIN
CALCIUM
CALCIUM 45
CALCIUM ISOTOPES
CARDIOVASCULAR AGENTS
CARDIOVASCULAR DISEASES
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELEMENTS
ENZYME INHIBITORS
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYPERTENSION
IMIDAZOLES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MEMBRANES
METALS
NERVOUS SYSTEM
NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PATHOGENESIS
PORINS
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SYMPATHOMIMETICS
SYMPTOMS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASCULAR DISEASES
VASOCONSTRICTORS
VERTEBRATES