Role of calcium in postjunctional supersensitivity.

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Cellular Biology

Background:

• Reserpine administration induces cardiovascular supersensitivity to catecholamines in animals.
• This supersensitivity is observed in vascular tissue and affects responses to various agonists.
• Reserpine treatment is associated with a transient decrease in vascular tissue calcium content.

Purpose of the Study:

• To investigate the role of calcium in reserpine-induced cardiovascular supersensitivity.
• To elucidate the mechanisms underlying the altered responses to catecholamines and other agonists.
• To determine how reserpine affects calcium binding and movement in vascular tissues.

Main Methods:

• In vitro experiments on aortic strips from reserpine-treated and untreated rabbits.
• Assessment of tissue responses to norepinephrine, acetylcholine, calcium, and potassium.
• Studies using calcium-free media to evaluate extracellular calcium dependence.
• Tension decline and 45Ca efflux assays to analyze calcium dynamics.

Main Results:

• Reserpine-treated aortic strips showed enhanced responses to norepinephrine but were less dependent on extracellular calcium.
• Responses to potassium were more dependent on extracellular calcium and lost supersensitivity in calcium-free conditions.
• Supersensitivity to norepinephrine and isoproterenol persisted in calcium-free media, unlike acetylcholine.
• Reserpine-treated tissues retained a calcium fraction involved in contraction longer than controls.

Conclusions:

• Reserpine alters calcium binding or movement at multiple sites within vascular tissue.
• The drug affects extracellular calcium utilization, particularly for acetylcholine and potassium responses.
• Different mechanisms underlie supersensitivity to catecholamines versus other agonists, involving distinct calcium pools.