Endothelium-independent and -dependent vasodilation in alkalotic and acidotic piglet lungs

Abstract

Although significant pulmonary hypertension can occur in patients treated with either hypocapnic alkalosis or “permissive” hypercapnic acidosis, the effects of sustained alkalosis or acidosis on subsequent vasodilator responses have not been established. This study measured the effects of 60–100 min of sustained alkalosis or acidosis on endothelium‐independent and ‐dependent vasodilation with inhaled nitric oxide (iNO) and acetylcholine (ACh) in isolated lungs from 1‐week‐old piglets. After stabilization, lungs were divided into control (pH 7.40, PaCO2 40 torr, n = 5), alkalotic (pH 7.60, PaCO2 25 torr, n = 6), or acidotic (pH 7.25, PaCO2 65 torr, n = 5) groups and ventilated with 21% O2 for 40 min. Acute hypoxic pulmonary vasoconstriction (HPV) was then induced with 4–6% O2. After a stable pressor response had occurred (≊mF20 min), pulmonary artery dose‐response relationships to increasing concentrations of iNO were measured. The iNO was then stopped and after a stable hypoxic pressure had again been reestablished (≊mF20 min), dose‐responses to increasing concentrations of ACh were measured. Hypoxic pulmonary vascular resistance (PVR) was similar in all groups. Pulmonary artery pressure dose‐response relationships to iNO and ACh were blunted in the alkalosis group, suggesting that both endothelium‐independent and ‐dependent vasodilation were reduced during sustained hypocapnic alkalosis. In contrast, sustained acidosis did not alter subsequent vasodilator responses. Future studies must elucidate the mechanisms underlying blunted pulmonary vasodilation during sustained alkalosis and examine the consequences of sustained alkalosis therapy on subsequent vasodilator responses in clinical practice. Pediatr Pulmonol. 2000; 30:241–248. © 2000 Wiley‐Liss, Inc.

Effect of voluntary hypocapnic hyperventilation on the relationship between core temperature and heat loss responses in exercising humans

“…Esophageal temperature, cutaneous vascular conductance, and sweat rate. Although there was a main effect of time on esophageal temperature [F (4,36) ϭ84.2, P Ͻ 0.001] and forehead cutaneous vascular conductance [F (4,36) ϭ22.4, P Ͻ 0.001], no interactions [both F (8,72) Ͻ1.74, P Ͼ 0.104] and no main effect of ventilatory condition [both F (2,18) Ͻ2.07, P Ͼ 0.156] on esophageal temperature or forehead cutaneous vascular conductance were seen, indicating that esophageal temperature and forehead cutaneous vascular conductance did not differ between trials at any time point (Fig. 2, A and C).…”

“…An interaction was observed between the effects of ventilatory condition and time on mean skin temperature, heart rate, and middle cerebral artery vascular conductance index [all F (8,72) Ͼ2.27, P Ͻ 0.032], while main effects of ventilatory condition on forearm skin temperature [F (2,18) ϭ 4.02, P ϭ 0.036] and of time on forearm and forehead skin temperature and mean arterial pressure were detected [all F (4,36) Ͼ 4.11, P Ͻ 0.008]. During voluntary hyperventilation at rest or during exercise, mean skin temperature, forearm skin temperature, heart rate, and middle cerebral artery vascular conductance index were all lower in the hypocapnic hyperventilation trial than in the spontaneous ventilation or normocapnic hyperventilation trial (Table 1).…”

“…ACh and neuropeptides released from cholinergic nerve terminals during hyperthermia bind to receptors on vessels in the skin, inducing vasodilation (25,26,45). Hypocapnia may blunt the responsiveness of those vessels to ACh, as was seen in the pig pulmonary artery (4). Two other mediators involved in cutaneous vasodilation during hyperthermia are nitric oxide and substance P (45,55).…”

“…Two other mediators involved in cutaneous vasodilation during hyperthermia are nitric oxide and substance P (45,55). Hypocapnia may lower cutaneous vascular responsiveness to nitric oxide and substance P, as it does in pulmonary artery from pigs and airway smooth muscle from rats (4,14). In addition, intracellular alkalosis increases vascular smooth muscle contractility through several mechanisms, including increasing levels of intracellular Ca 2ϩ (16).…”

Effect of voluntary hypocapnic hyperventilation on cutaneous circulation in resting heated humans

“…This active cutaneous vasodilation also involves several of substances in addition to ACh (45), including nitric oxide (NO) (28,42), histamine (57), prostaglandins (33) and potentially substance P (56). Moreover, the observation that, in animals, hypocapnia attenuates the vasodilatory responses to NO (2), ACh (2), and substance P (10) suggests hypocapnia may attenuate the nonglabrous cutaneous vasodilatory response to heat stress in humans, as it does the sweat response (1). Accordingly, the present study was designed to test the hypothesis that in resting heated humans, hypocapnia induced by voluntary hyperventilation attenuates the increase in blood flow to nonglabrous skin.…”