The effect of chronic and acute administration of deuterium oxide (D2O) on vascular smooth muscle contraction in spontaneously hypertensive and Wistar-Kyoto rats.

1. Oral administration of 25% D2O for 12 days reduced blood pressure of spontaneously hypertensive rats (SHR) to the level of Wistar-Kyoto (WKY) controls. 2. However, the chronic D2O treatment appeared to have little effect on the phenylephrine and potassium chloride induced dose-response curves of SHR and WKY rats, producing a decreased maximal contraction of the potassium chloride dose-response curve of SHR only. 3. Further acute studies revealed that desensitization results from chronic exposure to D2O such that 60% D2O produces a significant depression of contraction only in aortic rings obtained from SHR and WKY which had not been chronically treated with 25% D2O.

Deuterium oxide reduces agonist and depolarization-induced contraction of rat aortic rings.

The influence of deuterium oxide (D2O) on calcium-dependent vascular smooth muscle contraction was investigated. The effect of D2O on receptor-operated calcium channels was investigated with phenylephrine-induced contraction in the rat aortic ring preparation. D2O depressed the contraction response in a dose-dependent manner with 50% inhibition of maximum contraction observed with 60% D2O. The effect of 60% D2O on phenylephrine-induced contraction was reversible and not dependent on an intact endothelium. Sixty percent D2O also reduced potassium chloride induced contractions by 50%, indicating an effect on voltage-operated calcium channels. Studies with Bay K 8644, and L-type calcium channel activator, confirm an effect on utilization of extracellular calcium sources and on the voltage-operated calcium channel. Sixty percent D2O also depressed a calcium contraction dose-response curve by approximately 25%. Likewise, a change in the pD2' for nifedipine in the presence of D2O may indicate an effect on the nifedipine binding site and (or) the voltage-dependent calcium channel. Further studies were performed to determine whether the D2O effects were nonspecific or selective effects on the receptor- and voltage-operated calcium channels. Sucrose-induced contaction in the presence of 60% D2O was found to be inhibited by approximately 50%. D2O similarly affected isoprenaline relaxation, which would suggest a nonspecific D2O effect on the vascular smooth muscle contractile process.

Studies of the desensitization of atrial natriuretic factor and nitroglycerin in rat aortic rings.

1. Atrial natriuretic factor (ANF) relaxes vascular smooth muscle through activation of particulate guanylate cyclase and generation of cyclic GMP. 2. From other laboratories, there is some evidence from cultured vascular smooth muscle cell studies for homologous desensitization of ANF-induced cGMP production and down-regulation of ANF receptors. 3. This series of studies demonstrates that homologous desensitization of ANF-induced relaxation of rat aortic ring preparations also occurs. 4. Heterologous desensitization could not be demonstrated to the vasoactive peptides angiotensin II or vasopressin, nor to nitroglycerin which has previously been shown to exhibit heterologous desensitization with other nitrovasodilators and shares some common elements in the pathway to vascular smooth muscle relaxation with ANF.