15-hydroxy-11-alpha-9-alpha-(epoxymethano)prosta-5-13-dienoic-acid and Acidosis

Changes in pH can have profound effects on vascular tone and reactivity, but their influence on the ductus arteriosus (DA) remains unknown.. To analyzethe effects of hypercarbic and normocarbic acidosis in the reactivity of the chicken DA.. DA rings from 19-day chicken fetuses (total incubation time, 21 days) were mounted in a wire myograph for isometric tension recording.. In DA rings (pulmonary side) stimulated with O(2), norepinephrine (NE), KCl, or U46619, changes from control conditions (5% CO(2), 24 mM NaHCO(3), pH 7.4) to 7.5% CO(2) (pH 7.25) or 10% CO(2) (pH 7.14) induced a concentration-dependent relaxation that reached 43.0% (SD 21.3) of the O(2)-, 28.6% (SD 23.1) of the NE-, 10.4% (SD 18.7) of the KCl-, and 6.8% (SD 12.6) of the U46619-induced contraction. Hypercarbic-acidosis-induced relaxation was impaired by the non-selective K(+) channel blocker tetraethylammonium or the BK(Ca) channel inhibitor iberiotoxin. Normocarbic acidosis (5% CO(2), 12 mM NaHCO(3), pH 7.13) induced transient relaxation of the DA, which was not affected by the presence of tetraethylammonium or iberiotoxin. Euhydric hypercarbia (10% CO(2), 48 mM NaHCO(3), pH 7.46) induced a transient contraction of the DA.. Our results indicate that the chicken DA is very sensitive to changes in extracellular pH, and that stimulation of BK(Ca) channels may account for the ductal-relaxing effects of hypercarbic acidosis.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acidosis; Animals; Carbon Dioxide; Chick Embryo; Ductus Arteriosus; Hydrogen-Ion Concentration; Hypercapnia; Norepinephrine; Peptides; Potassium Channel Blockers; Potassium Channels; Tetraethylammonium

Carbonic anhydrase inhibitors reduce intraocular pressure, which may protect the optic nerve from ischemia. However, carbonic anhydrase inhibitors have also been shown to dilate the blood vessels in the retina and the optic nerve head. The purpose of the present study was to investigate whether CO(2), H(+), or factors other than carbonic anhydrase inhibition are involved in this vasodilating effect.. Porcine retinal arterioles with preserved perivascular retinal tissue were mounted in a myograph for isometric force measurements. After precontraction with the prostaglandin analogue U46619, concentration-response experiments were performed with acetazolamide and dorzolamide before and after removal of the perivascular retina. The experiments were performed at normal pH and during acidosis, during normocapnia and hypercapnia, as well as in the nominal absence of CO(2) and HCO(3)(-).. The maximum relaxation was significantly lower and the EC(50) significantly higher during normal pH compared with acidosis (P = 0.002 and P < 0.0001, respectively), but neither the maximum relaxation nor EC(50) was changed by hypercapnia (P = 0.054 and P = 0.57, respectively). The findings confirmed that carbonic anhydrase-induced vasodilation depends on the perivascular retinal tissue and that dorzolamide produces significantly more pronounced relaxation than does acetazolamide. EC(50) of carbonic anhydrase inhibitor-induced vasorelaxation and the maximum relaxation of dorzolamide were unchanged in the nominal absence of CO(2) and HCO(3)(-) (P = 0.65 and P < 0.0001, respectively).. The vasodilating effect of carbonic anhydrase inhibitors on porcine retinal arterioles depends on the perivascular retinal tissue and acidosis, but not on hypercapnia. The effect involves mechanisms other than carbonic anhydrase inhibition.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acetazolamide; Acidosis; Animals; Arterioles; Carbon Dioxide; Carbonic Anhydrase Inhibitors; Carbonic Anhydrases; Dose-Response Relationship, Drug; Hydrogen-Ion Concentration; Hypercapnia; Muscle, Smooth, Vascular; Myography; Nifedipine; Retinal Artery; Sulfonamides; Swine; Thiophenes; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Respiratory or renal failure is associated with changes in blood pH. Changes in pH may have profound effects on vascular tone and reactivity. Site of action of acidosis in the pulmonary vasculature and the role of nitric oxide production remain unclear.. We utilized isolated rat lung preparation perfused with autologous blood (Hct = 20%, flow rate = 33 ml/min), and investigated the effect of acidosis and alkalosis (induced by ventilation with high and low inspired CO2) on vascular resistance and the role of nitric oxide during resting and elevated tone conditions. Changes in resistance were described in terms of small and large arteries and veins, using the vascular occlusion technique.. Acidosis (Pco2 = 66.7 +/- 0.7 mmHg, pH = 7.17 +/- 0.01, Po2 = 255 +/- 3 mmHg) caused vasoconstriction under resting and increased vascular tone conditions (U46619-induced). The changes in resistance occurred primarily in the small arteries. In contrast, alkalosis (Pco2 = 20.1 +/- 0.3 mmHg, pH = 7.61 +/- 0.01, Po2 = 244 +/- 3 mmHg) caused vasodilation only at elevated tone conditions. Nitro-L-arginine (LNA), an inhibitor of nitric oxide synthase, increased vascular resistance slightly but did not modulate the responses to pH, suggesting that such responses are not nitric oxide dependent. During KCl-induced contraction, the effects of pH were abolished.. We conclude that in rat lung, acidosis causes an increase in pulmonary vascular resistance at normal and elevated tone conditions. Furthermore, the response is limited primarily to the small arteries, and is not mediated by nitric oxide. Alkalosis tends to cause the opposite effects. The effects of acidosis and alkalosis were abolished when vascular tone was elevated with a low dose of KCl, suggesting that vascular response to pH may involve changes in membrane potential.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acidosis; Alkalosis; Analysis of Variance; Animals; Enzyme Inhibitors; Hydrogen-Ion Concentration; Hypercapnia; Hypocapnia; Lung; Male; Microcirculation; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Potassium Chloride; Pulmonary Artery; Pulmonary Veins; Rats; Rats, Sprague-Dawley; Renal Insufficiency; Respiratory Insufficiency; Vascular Resistance; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Using an isolated rat heart preparation and 31P magnetic resonance spectroscopy, we studied the effects of endothelin-1 (ET-1) and U-46619, a thromboxane-A2 analogue, on coronary flow (CF), left ventricular developed pressure (LVP), and high-energy phosphate metabolism under control conditions (normal myocardium) and during postischemic reperfusion (reperfused myocardium). The selected doses of ET-1 and U-46619 reduced CF in the normal myocardium to a similar extent (47.8 +/- 1.5% and 48.7 +/- 4.6%, respectively). In contrast to ET-1, U-46619 induced a depression of LVP (20.2 +/- 6.9% versus 6.8 +/- 4.7%; p < 0.05) which was accompanied by an intracellular acidosis, indicating that a low-flow ischemia occurred. In reperfused hearts, the ET-1-induced decrease in CF was more pronounced compared to U-46619 (79.5 +/- 1.6% versus 59.0 +/- 5.9%; p < 0.05) and to ET-1-induced decrease in CF in the normal myocardium (74.0 +/- 7.9% versus 32.4 +/- 6.3%; p < 0.05). This was accompanied by a large decrease in LVP and in levels of high-energy phosphate compounds. Therefore, the effects of ET-1 but not of U-46619 are enhanced in reperfused hearts. This may contribute to the delayed recovery of the postischemic reperfused myocardium.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acidosis; Adenosine Triphosphate; Animals; Coronary Circulation; Endothelins; Heart; Hydrogen-Ion Concentration; In Vitro Techniques; Magnetic Resonance Spectroscopy; Myocardial Reperfusion Injury; Myocardium; Prostaglandin Endoperoxides, Synthetic; Rats; Rats, Sprague-Dawley; Thromboxane A2; Vasoconstrictor Agents; Ventricular Function, Left