To test the hypothesis that cutaneous active vasodilation in heat stress is mediated by a redundant cholinergic cotransmitter system, we examined the effects of atropine on skin blood flow (SkBF) increases during heat stress in persons with (CF) and without cystic fibrosis (non-CF). Vasoactive intestinal peptide (VIP) has been implicated as a mediator of cutaneous vasodilation in heat stress. VIP-containing cutaneous neurons are sparse in CF, yet SkBF increases during heat stress are normal. In CF, augmented ACh release or muscarinic receptor sensitivity could compensate for decreased VIP; if so, active vasodilation would be attenuated by atropine in CF relative to non-CF. Atropine was administered into skin by iontophoresis in seven CF and seven matched non-CF subjects. SkBF was monitored by laser-Doppler flowmetry (LDF) at atropine treated and untreated sites. Blood pressure [mean arterial pressure (MAP)] was monitored (Finapres), and cutaneous vascular conductance was calculated (CVC = LDF/MAP). The protocol began with a normothermic period followed by a 3-min cold stress and 30-45 min of heat stress. Finally, LDF sites were warmed to 42 degrees C to effect maximal vasodilation. CVC was normalized to its site-specific maximum. During heat stress, CVC increased in both CF and non-CF (P < 0.01). CVC increases were attenuated by atropine in both groups (P < 0.01); however, the responses did not differ between groups (P = 0.99). We conclude that in CF there is not greater dependence on redundant cholinergic mechanisms for cutaneous active vasodilation than in non-CF.

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Endothelin-1 (ET-1) is relevant to the pathogenesis of pulmonary arterial hypertension (PAH) in several species, including broiler chickens. In ET-1-induced vasoconstriction, L-type voltage-operated calcium channels (VOCCs) play a crucial role. In this study, the effect that ET-1 and the calcium channel blocker (CCB) nifedipine have on ET-1-induced vascular contraction in pulmonary artery rings of both, nonpulmonary hypertensive chickens (NPHC) and pulmonary hypertensive chickens (PHC), was evaluated. A significant increase response in ET-1 was observed for PHC vascular rings with respect to those of NPHC (p < .05). Incubation with 1 μM nifedipine did not completely reverse the contraction induced by 1 × 10 −7 M ET-1 in both NPHC and PHC rings, suggesting the participation of additional calcium sources procured via influx through L-type VOCC. Nifedipine reduced, to a higher degree, the contraction induced by ET-1 in NPHC (50%) when compared with that observed in PHC rings (30.7%). Thus, the ET-1-induced vasoconstriction processes are more efficient in PHC, and the influx of calcium into the cell through the L-type VOCC is presumably only a fraction of the necessary calcium for ET-1-induced vasoconstriction. It is suggested that blocking calcium uptake through alternative pathways (receptor-operated calcium channels and storage-operated calcium channels) may produce a vasodilation effect of considerable therapeutic significance in PHC. ARTICLE HISTORY

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