Cornell Research Foundation Inc.

University of Texas System

Roberto Levi

Steven S Gross

Owen W Griffith

Robert G Kilbourn

Randi B Silver

The invention provides a method for reducing cardiac dysfunctions in a human. The method comprises administration to the human of an effective amount of a selective histamine HReceptor agonist. In one embodiment, the method comprises limiting the accumulation of intracellular sodium (Na) by inhibiting the Na/Hexchanger activity in the human having a cardiac dysfunction, or a predisposition to a cardiac dysfunction. In another embodiment the method comprises inhibiting the N-type Cachannel to modulate the concentration of intracellular calcium. The invention also provides a pharmaceutical composition that includes a selective histamine HReceptor agonist with a pharmaceutical carrier.

Method and compositions for reducing cardiac dysfunctions with a selective histamine H3 receptor agonist

A method for prophylaxis or treatment of an animal for systemic hypotension induced by internal nitrogen oxide production. The method involves administering a therapeutically effective amount of certain arginine derivatives to inhibit nitrogen oxide formation from arginine. Preferably N.sup.G -substituted arginine or an N.sup.G,N.sup.G -disubstituted arginine (having at least one hydrogen on a terminal guanidino amino group replaced by another atomic species) is administered to an animal possibly developing or already having such induced systemic hypotension. The arginine derivatives are preferably of the L configuration and include pharmaceutically acceptable addition salts. Prophylaxis or treatment of systemic hypotension in a patient which has been induced by chemotherapeutic treatment with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, i.e., septic shock may also be accomplished by treatment with the arginine derivatives.

Argine antagonists for inhibition of systemic hypotension associated

Reducing plasma levels of endogenous arginine by parenteral administration of arginine depleting agent limits nitric oxide formation and results in blood pressure increase. Preferably arginase is administered intravenously to raise blood pressure. The arginine depleting agent can be administered in conjunction with arginine antagonists to potentiate the effect of these. The arginine depleting agent can be used concurrently with .alpha..sub.1 adrenergic agonists in treating systemic hypotension caused by induced production of nitric oxide, to restore vascular contractile sensitivity to the effect of the .alpha..sub.1 adrenergic agonists. Duration of action and avoidance of antigenicity may be obtained by use in conjunction with a carrier or modifier.

Method for treating systemic hypotension caused by sepsis or cytokine

A method for treatment of an animal for systemic hypotension induced by internal nitric oxide production caused by endotoxin or cytokines. The method involves administering an .alpha..sub.1 adrenergic agonist and an amount of an inhibitor of nitric oxide formation from argi

Nitric oxide synthesis inhibitors for potentiating the action of pressor

A method for prophylaxis of treatment of an animal for systemic hypotension induced by internal nitrogen oxide production. The method involves administering a therapeutically effective amount of certain arginine derivatives to inhibit nitrogen oxide formation from arginine. Preferaby N.sup.G -substituted arginine or an N.sup.G,N.sup.G -disubstituted arginine (having at least one hydrogen on a terminal guanidino amino group replaced by another atomic species) is administered to an animal possibly developing or already having induced systemic hypotension. The arginine derivatives are preferably of the L configuration and include pharmaceutically acceptable addition salts. Prophylaxis or treatment or systemic hypotension in a patient which has been induced by chemotherapeutic treatment with biologic response modifiers such as tumor necrosis factor or interleukin-2 may be accomplished. Treatment of an animal for systemic hypotension induced by endotoxin, i.e., septic shock may also be accomplished by treatment with the arginine derivatives.

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Roberto Levi