Method and kit for regulation of microvascular tone

Abstract

Methods and kits for regulating arterial microvascular tone in which a COX-2 inhibitor and a cannabinoid receptor agonist are co-administered to a subject.

1 . A method for causing constriction of arterial microvasculature comprising co-administering to a vertebrate subject an effective amount of a cannabinoid receptor agonist and a COX-2 inhibitor.  
     
     
         2 . The method of  claim 1  wherein the subject is a mammal.  
     
     
         3 . The method of  claim 2  wherein the mammal is a human.  
     
     
         4 . The method of  claim 1  wherein the COX-2 inhibitor is also a COX-1 inhibitor.  
     
     
         5 . The method of  claim 1  wherein the COX-2 inhibitor is also a cannabinoid receptor agonist.  
     
     
         6 . The method of  claim 1  wherein the co-administration of the cannabinoid receptor agonist and the COX-2 inhibitor is by administering a single compound having both cannabinoid receptor agonist activity and COX-2 inhibitory activity.  
     
     
         7 . The method of  claim 1  wherein the COX-2 inhibitor is selected from the group consisting of rofecoxib, celecoxib, valdecoxib, paracoxib, etoricoxib, and NS-398.  
     
     
         8 . The method of  claim 1  wherein the cannabinoid receptor agonist is selected from the group consisting of Δ 9 -tetrahydrocannabinol, Δ 8 -tetrahydrocannabinol, anandamide, 2-arachidonyl glycerol, and methanandamide.  
     
     
         9 . The method of  claim 1  wherein the cannabinoid receptor agonist is a synthetic cannabinoid receptor agonist.  
     
     
         10 . The method of  claim 1  wherein the administration of the cannabinoid receptor agonist and the COX-2 inhibitor is systemic.  
     
     
         11 . The method of  claim 1  wherein the microvasculature is striated muscle microvasculature.  
     
     
         12 . A method for increasing blood pressure in a subject comprising co-administering an effective amount of a cannabinoid receptor agonist and a COX-2 inhibitor in an amount effective to increase blood pressure in the subject.  
     
     
         13 . The method of  claim 12  wherein the subject is a mammal.  
     
     
         14 . The method of  claim 13  wherein the mammal is a human.  
     
     
         15 . The method of  claim 12  wherein, at the time of the co-administration, the subject is suffering from an acute decrease in blood pressure.  
     
     
         16 . The method of  claim 12  wherein the co-administration is by administering a chemical compound that has activity as a cannabinoid receptor agonist and activity as a COX-2 inhibitor.  
     
     
         17 . A method for treating a subject suffering from or at risk of developing shock comprising co-administering to a vertebrate subject in need thereof a cannabinoid receptor agonist and a COX-2 inhibitor.  
     
     
         18 . The method of  claim 17  wherein the COX-2 inhibitor is also a COX-1 inhibitor.  
     
     
         19 . The method of  claim 17  wherein the co-administration is by administering a chemical compound that has activity as a cannabinoid receptor agonist and activity as a COX-2 inhibitor.  
     
     
         20 . The method of  claim 17  wherein the COX-2 inhibitor is selected from the group consisting of rofecoxib, celecoxib, valdecoxib, paracoxib, etoricoxib, and NS-398.  
     
     
         21 . The method of  claim 17  wherein the cannabinoid receptor agonist is selected from the group consisting of Δ 9 -tetrahydrocannabinol, Δ 8 -tetrahydrocannabinol, anandamide, 2-arachidonyl glycerol, and methanandamide.  
     
     
         22 . The method of  claim 17  wherein the cannabinoid receptor agonist is a synthetic cannabinoid receptor agonist.  
     
     
         23 . The method of  claim 17  wherein the administration of the cannabinoid receptor agonist and the COX-2 inhibitor is systemic.  
     
     
         24 . The method of  claim 17  wherein the subject is a mammal.  
     
     
         25 . The method of  claim 24  wherein the mammal is a human.  
     
     
         26 . The method of  claim 17  wherein the shock is hemorrhagic shock.  
     
     
         27 . The method of  claim 17  wherein the co-administration is to control hypotension associated with anesthetic agents.