Role of Bradykinin in Human Sweating During Stimulated and Actual Heat Stress

Bradykinin, a local dermal kallikrein-kinin system product, increases skin blood flow via a cyclic GMP mechanism but is not the active cutaneous vasodilation molecule associated with cholinergic stimulation. However, the precise role of bradykinin in sweating and thermoregulation is unclear. We tested the hypothesis that bradykinin increases eccrine sweating via increases in cutaneous capillary permeability and fluid extravasation. Protocol #1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46-48°C) water through a high-density tube-lined suit to induce heat stress. During heating a bradykinin type 2 (B2) receptor antagonist (HOE-140; 40μM) and the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis, while sweating (capacitance hygrometry) and cutaneous vascular conductance (CVC; Doppler flux/ mean arterial pressure) were obtained directly superficial to the membrane. In addition, both microdialysis membranes were then perfused with bradykinin (1mM). Protocol #2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing a cholinergic agonist (pilocarpine; 1.67 mg/ml) to mimic heat stress and steady state sweating conditions and was followed by the same B2 antagonist and agonist approach. Increases in internal (37.1±0.1 to 37.9±0.1°C) and uncovered local skin (30.1±0.4 to 32.9±0.4°C) temperature caused increases in sweat rate (+0.79±0.12 and +0.64±0.10 mg/cm2/min) and CVC (63±11 to 181±22 and 85±15 to 204±19 flux/ mmHg for HOE-140 and vehicle, respectively), while HOE-140 and control sites were not different. Heart rate increased (62±3 to 94±6 bpm) with whole-body heating but arterial blood pressure was not significantly altered. Pilocarpine induced sweating (+0.38±0.16 and +0.32±0.12 mg/cm2/min) and increases in CVC (88±36 to 183±55 and 73±25 to 208±66 flux/mmHg for HOE-140 and vehicle, respectively) but again, no changes between sites were noted. These data indicate that B2 receptor antagonists do not modulate physiological or pharmacological sweating. HOE-140 delivered during normothermia was also identified not to be sudorific. The addition of exogenous bradykinin also did not modulate sweating during whole-body heating or pilocarpine perfusion in either control or HOE-140 sites. These data indicate HOE-140 does not affect sweating independently and B2 agonists do not modulate absolute sweat output. Although the kallikrein-kinin system is present in eccrine sweat glands, its precise role remains to be elucidated. Current data do not support a mechanism related to absolute in vivo sweat output and evaporative cooling but rather its role may be more conditionspecific or supportive to epithelial transport and the alteration of the interstitial milieu around the gland