Date of Award

5-1-1986

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Laboratory Science

Abstract

Two of the major effects of histamine in the rabbit heart are the enhancement of contractility and microvascular permeability. In cardiac muscle it has been documented that calcium (Ca ) bound to the sarcolem- mal-glycocalyx complex is essential for the regulation of the contractile response. In addition, it has been postulated that histamine's regulation of microvascular permeability may occur via an endothelial contractile response causing the formation of submicroscopic gaps between endothelial cells. It was postulated that these effects of histamine may in- O . volve an alteration of Ca r binding to the plasma membranes of these tissues. In previous work I have shown that the calcium channel blocker verapamil inhibits lanthanum (La^+) binding to the cellular surface in the isolated rabbit heart, La^+ being used as an electron opaque marker for Ca ’r binding sites. For the present study I reasoned that if hista- O i mine increases cellular contractility by enhancing Ca binding to the O i plasma membrane, it may cause the reappearance of La r binding to the cell membrane in the presence of verapamil. I examined this by first perfusing rabbit hearts with histamine (1.1 x 10“^ M) for 3 min, secondly with histamine and verapamil (10-^ M) for 30 min, and subsequently with histamine in the presence of La^+ (10 mM) and verapamil for 30 min. Subsequent transmission electron microscopy revealed the presence of bound La on both the cellular surface and cytoplasmic vesicles of cardiac myocytes and vascular endothelial cells which is in contrast to the ab- sence of La T binding that occurs in the presence of verapamil alone. This visual evidence of an apparent enhancement of La^+ binding under histamine supports the hypothesis that histamine may exert its effects by causing increased Ca 'r binding to the plasma membranes of cardiac and vascular endothelial cells in rabbit myocardium. Further work character- O . O . ized the type of histamine receptors affecting La r (Ca ‘r) by use of appropriate pharmacological agents. Treatment of hearts with the H^-recep- —7 3+ tor blocker diphenhydramine (3.4 x 10 M) prior to histamine reduced La "r binding to vascular endothelium but not myocardium. Treatment of hearts with the H^-receptor blocker cimetidine (4.0 x 10“^ M) prior to histamine O . reduced La binding to both cell types.

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