oxadiazoles and Alkalosis

Pulmonary venous constriction leads to significant pulmonary hypertension and increased edema formation in several models using newborns. Although alkalosis is widely used in treating neonatal and pediatric pulmonary hypertension, its effects on pulmonary venous tone have not previously been directly measured. This study sought to determine whether alkalosis caused pulmonary venous relaxation and, if so, to identify the mediator(s) involved. Pulmonary venous rings (500-microm external diameter) were isolated from 1-wk-old piglets and precontracted with the thromboxane mimetic U-46619. Responses to hypocapnic alkalosis were then measured under control conditions after inhibition of endothelium-derived modulator activity or K(+) channels. In control rings, alkalosis caused a 34.4 +/- 4.8% decrease in the U-46619-induced contraction. This relaxation was significantly blunted in rings without functional endothelium and in rings treated with nitric oxide synthase or guanylate cyclase inhibitors. However, neither cyclooxygenase inhibition nor voltage-dependent, calcium-dependent, or ATP-dependent K(+)-channel inhibitors altered alkalosis-induced relaxation. These data suggest that alkalosis caused significant dilation of piglet pulmonary veins that was mediated by the nitric oxide-cGMP pathway.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; 4-Aminopyridine; Alkalosis; Animals; Cyclic GMP; Endothelium, Vascular; Enzyme Inhibitors; Glyburide; Hypoglycemic Agents; In Vitro Techniques; Nitric Oxide; Nitroarginine; Oxadiazoles; Peptides; Potassium Channels; Pulmonary Veins; Quinoxalines; Swine; Vasoconstrictor Agents; Vasodilation

A provocative test of coronary artery spasm caused by alkalosis was used to evaluate a possible anti-coronary artery spasm effect of molsidomine. The rapid infusion of an alkaline buffer followed by maximal voluntary hyperventilation in 10 patients with angina at rest led to the appearance of anginal pain and significant, transient ischemic changes of the ST segment resulting from alkalosis-induced coronary spasm. A second provocative test was performed under the same conditions, 24 hours later, after the administration of 4 mg of molsidomine. Molsidomine prevented the development of coronary artery spasm in 8 of the 10 patients in the study group. These preliminary results justify further clinical evaluation of molsidomine in the treatment of vasospastic angina.

Topics: Alkalosis; Blood Pressure; Coronary Vasospasm; Electrocardiography; Female; Heart Rate; Humans; Male; Middle Aged; Molsidomine; Oxadiazoles; Sydnones; Vasodilator Agents

A test provocation of coronary artery spasm by alkalosis was used to evaluate a possible anti-coronary artery spasm effect of molsidomine. The rapid infusion of an alkaline buffer followed by maximal voluntary hyperventilation in 10 patients with angina at rest led to the appearance of angina pain and significant, transient ischaemic changes of the ST segment, due to alkalosis induced coronary spasm. A second provocation test was performed under the same conditions, 24 hours later, after the prior administration of 4 mg of molsidomine. Molsidomine prevented the development of coronary artery spasm in 8 of the 10 patients in the study group. These preliminary results justify further clinical evaluation of molsidomine in the treatment of vasospastic angina.

Topics: Alkalosis; Coronary Vasospasm; Electrocardiography; Female; Humans; Male; Middle Aged; Molsidomine; Oxadiazoles; Sydnones