Upregulation of Type III endothelial cell nitric oxide synthase by rho GTPase function inhibitors

A method for increasing endothelial cell Nitric Oxide Synthase activity in a subject to treat a condition favorably affected by an increase in endothelial cell Nitric Oxide Synthase activity in a tissue comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said tissue of the subject, provided that the rho GTPase function inhibitor is not an agent selected from the group consisting of a HMG-CoA reductase inhibitor a protein kinase C inhibitor, a tyrosine kinase inhibitor, and cyclosporin.

A method for reducing brain injury resulting from a stroke comprising:

• administering to a subject having an abnormally high risk of an ischemic stroke or having experienced an ischemic stroke, a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the brain tissue of the subject, provided that the rho GTPase function inhibitor is not an agent selected from the group consisting of a HMG-CoA reductase inhibitor, a protein kinase C inhibitor, a tyrosine kinase inhibitor, and cyclosporin.

A method for treating pulmonary hypertension comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the pulmonary tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for treating heart failure comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the heart tissue of the subject, provided that the rho GTPase function inhibitor is not an agent selected from the group consisting of a HMG-CoA reductase inhibitor, a protein kinase C inhibitor, a tyrosine kinase inhibitor and cyclosporin.

A method for treating progressive renal disease comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the kidney tissue of the subject, provided that the rho GTPase function inhibitor is not an agent selected from the group consisting of a HMG-CoA reductase inhibitor, a protein kinase C inhibitor, a tyrosine kinase inhibitor, and cyclosporin.

A method for treating a subject to increase blood flow in a tissue, comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the tissue of the subject, provided that the rho GTPase function inhibitor is not an agent selected from the group consisting of a HMG-CoA reductase inhibitor, a protein kinase C inhibitor and a tyrosine kinase inhibitor.

A method for treating a nonhyperlipidemic subject to increase endothelial cell Nitric Oxide Synthase activity in a tissue, comprising:

• administering to a nonhyperlipidemic subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for treating a subject with an abnormally low level of endothelial cell Nitric Oxide Synthase activity to increase endothelial cell Nitric Oxide Synthase activity in a tissue, comprising:

• administering to a subject with an abnormally low level of endothelial cell Nitric Oxide Synthase activity a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for treating a subject chronically exposed to hypoxic conditions to increase endothelial cell Nitric Oxide Synthase activity in a hypoxic tissue, comprising:

• administering to a subject chronically exposed to hypoxic conditions a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said hypoxic tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for treating a subject to increase endothelial cell Nitric Oxide Synthase activity in a tissue comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor and a substrate of endothelial cell Nitric Oxide Synthase, in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said tissue of the subject, provided that the rho GTPase finction inhibitor is not a HMG-CoA reductase inhibitor.

A method for treating a subject to increase endothelial cell Nitric Oxide Synthase activity in a tissue, comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor and a non-rho GTPase function inhibitor agent that increases endothelial cell Nitric Oxide Synthase activity, in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for increasing endothelial cell Nitric Oxide Synthase activity in a nonhyperlipidemic subject to treat a condition favorably affected by an increase in endothelial cell Nitric Oxide Synthase activity in a tissue comprising:

• administering to a nonhyperlipidemic subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for increasing endothelial cell Nitric Oxide Synthase activity in a subject to treat a hypoxia-induced condition favorably affected by an increase in endothelial cell Nitric Oxide Synthase activity in a hypoxic tissue comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said hypoxic tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for increasing endothelial cell Nitric Oxide Synthase activity in a subject to treat impotence favorably affected by an increase in endothelial cell Nitric Oxide Synthase activity in vascular tissue of the affected organ, comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said vascular tissue of the affected organ of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for increasing endothelial cell Nitric Oxide Synthase activity in a subject to treat a gastric motility disorder favorably affected by an increase in endothelial cell Nitric Oxide Synthase activity in an enteric tissue comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said enteric tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-COA reductase inhibitor.

A method for increasing endothelial cell Nitric Oxide Synthase activity in a subject to treat an esophageal motility disorder favorably affected by an increase in endothelial cell Nitric Oxide Synthase activity in an esophageal tissue comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in said esophageal tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for reducing brain injury resulting from a stroke in a nonhyperlipidemic subject, comprising:

• administering to a nonhyperlipidemic subject having an abnormally high risk of an ischemic stroke or having experienced an ischemic stroke, a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the brain tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for reducing brain injury resulting from a stroke in a subject, comprising:

• administering to a subject having an abnormally high risk of an ischemic stroke or having experienced an ischemic stroke, a rho GTPase function inhibitor and a substrate of endothelial cell Nitric Oxide Synthase, in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the brain tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for treating a nonhyperlipidemic subject to increase blood flow in a tissue, comprising:

• administering to a nonhyperlipidemic subject in need of such treatment a rho GTPase function inhibitor in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the tissue of the nonhyperlipidemic subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.

A method for treating a subject to increase blood flow in a tissue, comprising:

• administering to a subject in need of such treatment a rho GTPase function inhibitor and a substrate of endothelial cell Nitric Oxide Synthase, in an amount effective to increase endothelial cell Nitric Oxide Synthase activity in the tissue of the subject, provided that the rho GTPase function inhibitor is not a HMG-CoA reductase inhibitor.