Effects of a localized high-flow anastomosis between the aorta and left lower lobe pulmonary artery on great vessel flow and pulmonary arterial reactivity in the contralateral lung.

OBJECTIVES: We sought to assess the effects of a localized anastomosis between the aorta and left lower lobe pulmonary artery on flows through central vessels and on the vascular reactivity of small pulmonary arteries distal or contralateral to the shunt. METHODS: Flow rates in major vessels and tensions from small pulmonary arteries from the left and right lower lobes were determined 48 hours after creation of an end-to-side anastomosis of the left lower lobe pulmonary artery to the aorta. RESULTS: Anastomoses increased flow through the left lower lobe pulmonary artery from 194±6 to 452±18 mL/min immediately after anastomosis to 756±19 mL/min by the time of harvest (n=88, P<.05). Flow rates in main pulmonary arteries from hosts with anastomoses were lower (557±26 vs 1033±244 mL/min), whereas aortic root flows were not different from control values (1370±53 vs 1120±111 mL/min; P=.07). Wet/dry weights of both lungs and aortic flow rates were proportional to shunt flow rates. Pulmonary artery rings harvested from the right (unshunted) lobes of high-flow hosts exhibited increased reactivity to the thromboxane agonist U46619 and phenylephrine relative to those of left pulmonary arteries from the same animal or those of control hosts. CONCLUSIONS: Our studies are the first to identify enhanced reactivity of pulmonary arteries in a lung contralateral to a localized high-output shunt between an aorta and pulmonary artery. These observations suggest that patients with localized systemic-to-pulmonary shunt could exhibit modified vascular tone in remote pulmonary arteries.

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca2+ signaling and NO production in rat aorta.

Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or changed to a high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular Ca2+ ([Ca2+]i) in response to methacholine (10 microM) and histamine (10 microM) were significantly attenuated in aortic endothelial cells from rats fed a HS diet, whereas thapsigargin (10 microM)-induced increases in [Ca2+]i were unaffected. Methacholine-induced nitric oxide (NO) production was eliminated in endothelial cells of aortas from rats fed a HS diet. Low-dose ANG II infusion (5 ng x kg(-1) x min(-1) iv) for 3 days prevented impaired [Ca2+]i signaling response to methacholine and histamine and restored methacholine-induced NO production in aortas from rats on a HS diet. Adding Tempol (500 microM) to the tissue bath to scavenge superoxide anions increased NO release and caused N(omega)-nitro-L-arginine methyl ester-sensitive vascular relaxation in aortas from rats fed a HS diet but had no effect on methacholine-induced Ca2+ responses. Chronic treatment with Tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased methacholine-induced Ca2+ responses significantly in aortas from rats on a HS diet but not in aortas from rats on a LS diet. These findings suggest that 1) agonist-induced Ca2+ responses and NO levels are reduced in aortas of rats on a HS diet; 2) increased vascular superoxide levels contribute to NO destruction, and, eventually, to impaired Ca2+ signaling in the vascular endothelial cells; and 3) reduced circulating ANG II levels during elevated dietary salt lead to elevated superoxide levels, impaired endothelial Ca2+ signaling, and reduced NO production in the endothelium.

Salt-induced ANG II suppression impairs the response of cerebral artery smooth muscle cells to prostacyclin.

Recent studies have demonstrated that cerebral arteries from rats fed a high-salt (HS) diet exhibit impaired vasodilation and altered electrophysiological response to reduction in PO2. The present study examined whether an increase in salt intake alters the response of vascular smooth muscle cells (VSMC) to prostacyclin, a crucial mediator of hypoxic dilation in cerebral arteries. VSMC were isolated from cerebral arteries of male Sprague-Dawley rats maintained on an HS (4% NaCl) or a low-salt diet (0.4% NaCl) for 3 days. The stable prostacyclin analog iloprost (10 ng/ml) inhibited serotonin (0.1-10 microM)-induced contractions and the increase in intracellular Ca2+ concentration ([Ca2+]i) in VSMC isolated from arteries of animals fed the low-salt diet. In contrast, iloprost had no effect on serotonin-induced contractions and increases in [Ca2+]i in VSMC isolated from arteries of rats fed the HS diet. Preventing the fall in ANG in rats fed the HS diet by infusion of a low dose of ANG II (5 ng.kg(-1).min(-1) i.v.) restored the inhibitory effect of iloprost on serotonin-induced contractions and increases in [Ca2+]i in VSMC from animals fed the HS diet. These effects were reversed by AT1 receptor blockade with losartan. These results indicate that ANG II suppression secondary to elevated dietary salt intake impairs vascular relaxation and Ca2+ regulation by prostacyclin.