Fig. 1. Schematic illustrating non-neural, membrane, and intracellular mechanisms of vascular smooth muscle (VSM) control, which are potential targets for anesthetic action. Endogenously released nitric oxide (NO) is synthesized by NO synthase (eNOS) and diffuses across the VSM membrane to bind guanylate cyclase and mediate the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). cGMP phosphorylates protein kinase G, which stimulates membrane adenosine triphosphate–dependent (ATPase) pumps to transport calcium Ca2+into the extracellular space and the sarcoplasmic reticulum. Membrane-bound Ca2+-dependent and ATP-sensitive potassium (K+) channels contribute to the regulation of VSM transmembrane potential (Em) and thus to regulation of voltage-operated Ca2+channels. In turn, such regulation significantly affects intracellular calcium ([Ca2+]I), particularly in VSM. In the current study, effects of isoflurane on these mechanisms were examined by concurrent administration of analogs and inhibitors that are selective for different levels of VSM control. l-NAME inhibits formation of NO by NO synthase (NOS). ODQ inhibits guanylate cyclase–induced synthesis of cGMP. Rp-8-pCPT-cGMPS inhibits cGMP-induced activation of protein kinase G. SQ22536 inhibits adenylate cyclase–induced synthesis of cyclic adenosine monophosphate (cAMP). Rp-cAMPS inhibits cAMP-induced activation of protein kinase A (PKA). KCaand KATPchannels are blocked by iberiotoxin (IBX) and glybenclamide (Gly), respectively. 8-Br-cGMP and Sp-5,6-DCl-cBiMPS are membrane-permeable, hydrolysis-resistant cGMP and cAMP analogs, respectively.