Inhibitors of Nitric Oxide Synthase in Human Skin

Abstract

The aim of this study was to investigate in human skin in vivo the role of nitric oxide in maintaining resting vascular tone, in the vasodilatation caused by local warming and by ultraviolet B light exposure, and in the response to exogenous calcitonin gene-related peptide (CGRP). Cutaneous blood flow was assessed by planimetry of the visible erythema or pallor and by laser Doppler flowmetry. Intradermal injection of the inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol), into forearm skin produced a visible pallor and a reduction of blood flow at a controlled ambient temperature of 21 degrees C. The control, NG-nitro-D-arginine methyl ester (D-NAME; 25 nmol) or NG-monomethyl-L-arginine (L-NMMA; 25 nmol) did not cause pallor or reduce blood flow. L-NAME and L-NMMA caused dose- and time-dependent increases in pallor, and reductions in cutaneous blood flow in skin that had been locally warmed by immersion in water at 45 degrees C and in skin that had been exposed to ultraviolet B light. D-NAME and D-NMMA at comparable concentrations did not have the effects on skin blood flow observed with the L forms. L-NAME and L-NMMA both inhibited the increased blood flow in human skin caused by the intradermal injection of CGRP (12.5 or 25 pmol). The reduction of CGRP-induced increase of blood flow by L-NAME was reversed by L-arginine. Neither D-NAME nor D-NMMA inhibited the increase in blood flow caused by CGRP. Neither L-NAME nor L-NMMA inhibited the increase in blood flow in human skin caused by the intradermal injection of prostaglandin E2 (63 pmol). The data show that nitric oxide is involved in the maintenance of resting blood flow in human skin and also in the cutaneous vasodilator responses to local warming, ultraviolet B irradiation, or injection of CGRP.

Calcitonin Gene-Related Peptide8-37 Antagonizes Capsaicin-Induced Vasodilation in the Skin: Evaluation of a Human in Vivo Pharmacodynamic Model

“…This would suggest that in rabbit skin the vasodilator mechanism of CGRP is independent of NO, whereas NO may play an important role in the release of CGRP from capsaicin-sensitive nerves. In contrast, Goldsmith et al (1996) were able to inhibit CGRP-induced DBF increase by injecting L-NMMA into skin of the human forearm. Our findings indicate that, in the human skin, NO is neither involved in the release of CGRP nor in its vasodilator mechanism.…”

The Effect of the Nitric Oxide Synthase Inhibitor N-Nitro-<i>L</i>-Arginine-Methyl Ester on Neuropeptide-Induced Vasodilation and Protein Extravasation in Human Skin

“…Attenuation of electrically and mustard oil-induced neurogenic protein extravasation and vasodilation has been reported in some rodent studies [9, 10, 11, 12], whereas no significant role was found in others [13, 14]. Similarly, experiments in humans studying the role of NO on neuropeptide-induced vascular responses provide controversial results [15, 16, 17, 18]. The unequivocal results might reflect the complex interaction of NO and neuropeptides: there is evidence for neuropeptide-induced NO release, especially in the splanchnic vasculature [19].…”

Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a pet study with nitric oxide and cyclooxygenase inhibition

“…This is, however, masked in global blood flow measures, and the result is that total blood flow is seen to be reduced to a similar extent as the oxygen extraction is increased (and thus no changes in V O 2 are detected). Interestingly, in this respect, especially skin blood flow is pronouncedly decreased during NOS inhibition (7,11), but also resting blood flow in subcutaneous adipose tissue is largely dependent on NO (1). However, blood flow decreases in adipose tissue may not be the most important explanatory factor, since it was found in the current study that NOS inhibition at rest decreased adipose tissue blood flow to a similar degree as in muscle (Fig.…”