Lacy A. Holowatz

Nitric oxide is not permissive for cutaneous active vasodilatation in humans

The precise role of nitric oxide (NO) in cutaneous active vasodilatation in humans is unknown. We tested the hypothesis that NO is necessary to permit the action of an unknown vasodilator. Specifically, we investigated whether a low‐dose infusion of exogenous NO, in the form of sodium nitroprusside (SNP), would fully restore vasodilatation in an area of skin in which endogenous NO was inhibited during hyperthermia. This finding would suggest a ‘permissive’ role for NO in active vasodilatation. Eight subjects were instrumented with three microdialysis fibres in forearm skin. Sites were randomly assigned to (1) Site A: control site; (2) Site B: NO synthase (NOS) inhibition during established hyperthermia; or (3) Site C: NOS inhibition throughout the protocol. Red blood cell flux was measured using laser‐Doppler flowmetry (LDF) and cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was normalized to maximal vasodilatation at each site. In Site B, NG‐nitro‐l‐arginine methyl ester (l‐NAME) infusion during hyperthermia reduced CVC by ∼32 % (65 ± 4 % CVCmaxvs. 45 ± 4 % CVCmax; P < 0.05). Vasodilatation was not restored to pre‐NOS inhibition values in this site following low‐dose SNP infusion (55 ± 4 % CVCmaxvs. 65 ± 4 % CVCmax; P < 0.05). CVC remained significantly lower than the control site with low‐dose SNP infusion in Site C (P < 0.05). The rise in CVC with low‐dose SNP (ΔCVC) was significantly greater in Site B and Site C during hyperthermia compared to normothermia (P < 0.05). No difference in ΔCVC was observed between hyperthermia and normothermia in the control site (Site A). Thus, NO does not act permissively in cutaneous active vasodilatation in humans but may directly mediate vasodilatation and enhance the effect of an unknown active vasodilator.

Influence of Progestin Bioactivity on Cutaneous Vascular Responses to Passive Heating

PURPOSEnOral contraceptives influence the regulation of cutaneous vascular tone, and both estrogen and progesterone have been shown to affect nitric oxide (NO)-mediated vasodilation. We tested the hypothesis that cutaneous vascular conductance (CVC) during passive heating would be lower in women taking oral contraceptives with higher progestational bioactivity compared with those taking oral contraceptives with lower progestational bioactivity. We further hypothesized that this difference could be attributed to the relative degree of NO-dependent vasodilation.nnnMETHODSnFourteen women (20.3 +/- 0.3 yr) taking combined oral contraceptives (low progestin: 6 subjects, high progestin: 8 subjects) participated in a whole-body heating protocol and were tested during the end of active and placebo pill phases. Red blood cell (RBC) flux was measured by laser-Doppler flowmetry at a control microdialysis site (Ringers solution) and an experimental site where NO-synthase (NOS) was inhibited (10 mM L-NAME). CVC was calculated as RBC flux/MAP.nnnRESULTSnBaseline oral temperature (Tor) was significantly higher during the active pill phase for all subjects (active: 36.8 +/- 0.1 degrees C; placebo: 36.6 +/- 0.1 degrees C) (P = 0.02) but was not affected by progestational bioactivity. CVC at the control site during heating did not differ between low and high progestin users during either phase of oral contraceptive use. However, CVC in the NOS inhibited site was diminished during both phases of oral contraceptive use in the low progestin group at a given change in Tor (active: DeltaT(or) of 0.6-1.0 degrees C, placebo: DeltaT(or) of 0.8-1.0 degrees C) (P < 0.05). (DeltaT(or) 1.0 degree C: active: 30.86 vs 46.56%CVC(max); placebo: 26.29 vs 49.22% CVC(max)) (P < 0.05).nnnCONCLUSIONnProgestational activity in oral contraceptives may alter the mechanisms by which skin blood flow increases during passive heating via NO-dependent cutaneous active vasodilation.