The role of protein kinase G in the cutaneous vascular response to whole body heat stress in humans

Abstract

We tested the hypothesis inhibition of protein kinase G would attenuate active vasodilation to an extent similar to NO synthase (NOS) inhibition. Five subjects were instrumented with 3 microdialysis fibers were placed on the ventral forearm and each site randomly assigned a drug treatment: 1) lactated Ringer's (control; CON); 2) 10 mM L-NAME to inhibit NOS; 3) 16 mM of the PKG-inhibitor, Rp-cGMPS (Rp). All drugs were infused for 45 min, after which subjects underwent whole body heating (WBH) via water perfused suits sufficient to raise oral temperature 0.8°C above baseline. Systemic arterial pressure (SAP) was monitored and skin blood flow was measured via laser-Doppler flowmetry (LDF). At the end of WBH, subjects were cooled and peak skin blood flow was achieved via infusion of 56 mM nitroprusside and cutaneous vascular conductance (CVC) was calculated as SAP/LDF. Data were normalized to peak values (%CVCpeak). A larger than normal dose of nitroprusside was required to overcome inhibition of PKG. There was no statistical difference in raw peak CVC values. During WBH, CVC averaged 70±3 %CVCpeak in CON, 41±3 %CVCpeak in L-NAME (p < 0.01 vs. CON and Rp), and 55±4 %CVCpeak in Rp (p < 0.01 vs. CON). From these data it appears NO in AVD is working through both a PKG-dependent pathway as well as a PKG-independent pathway as evidenced by the greater reduction in AVD in L-NAME compared to Rp-cGMPS sites.