1 ) Both nitric oxide synthase 1 and soluble guanylate cyclase are expressed in higher levels in vascular tissues during sepsis ; 2 ) both proteins physically interact and nitric oxide synthase 1 blockade inhibits cyclic guanosine monophosphate production ; 3 ) pharmacological blockade of nitric oxide synthase 1 using 7-nitroindazole or S-methyl-L-thiocitrulline reverts the hyporesponsiveness to phenylephrine and increases the vasoconstrictor effect of norepinephrine and phenylephrine .