Increases in flow reduce the release of endothelium-derived relaxing factor in the aorta of normotensive and spontaneously hypertensive rats

Experiments were designed to compare basal and acetylcholine-induced release of endothelium-derived relaxing factor at different flow rates in the aorta of the normotensive (Wistar-Kyoto; WKY) and spontaneously hypertensive (SHR) rat. Aortic segments (with endothelium) of either WKY or SHR were perfused at different flow rates (1 or 4 mL/min) with modified Krebs-Ringer solution; the relaxing activity of the perfusate from the two types of segments was bioassayed by measuring the isometric force in rings (without endothelium, and contracted with norepinephrine) of aortas of both WKY and SHR. All studies were performed in the presence of indomethacin to prevent endothelial production of prostacyclin and other vasodilator prostanoids. The basal release of endothelium-derived relaxing factor was not significantly affected by the flow rate in either the WKY or the SHR aortas. At the two flow rates, and with both types of bioassay rings, the basal release of endothelium-derived relaxing factor was smaller with SHR than with WKY aortas, but this reached significance only at 4 mL/min using the SHR-aorta as bioassay tissue. Both with WKY and SHR aortas the release of endothelium-derived relaxing factor evoked by acetylcholine was significantly larger at 1 than at 4 mL/min; no significant differences in responsiveness to acetylcholine were noted between WKY and SHR segments. There was also no difference in responsiveness of WKY and SHR bioassay rings to acetylcholine and acetylcholine-induced release of endothelium-derived relaxing factor. These experiments suggest that prolonged exposure to increases in shear stress reduced the ability of the endothelium to release endothelium-derived relaxing factor in responses to muscarinic activation.link_to_subscribed_fulltex

Endothelium-dependent relaxing factors do not affect the smooth muscle of portal-mesenteric veins

Experiments were designed to analyze the difference in endothelium-dependent responsiveness to acetylcholine between arteries and veins. The effect of endothelium-derived relaxing factor(s) released from femoral arteries of the dog was compared on the coronary artery of the dog, the aorta of the rat, and portal-mesenteric veins of both species. Endothelium-derived relaxing factor(s) released by canine coronary femoral arteries induced comparable relaxation of the canine artery and the aorta of the rat. However, neither the canine nor the rat portal vein relaxed when exposed to endothelium-derived relaxing factor(s) released by the femoral arterial segments. Endothelium-derived relaxing factor(s) did not affect the action potentials and the spontaneous activity of the rat portal vein. Sodium nitroprusside induced complete relaxation of the canine coronary artery but failed to abolish the spontaneously evoked contractions of the portal veins. These experiments suggest that the longitudinal smooth muscle of portal veins is insensitive to endothelium-derived relaxing factor(s), presumably because of a different sensitivity of guanylate cyclase. Endothelium-derived relaxing factor does not possess calcium-entry blocking properties.link_to_subscribed_fulltex

Proximal and distal dog coronary arteries respond differently to basal EDRF but not to NO

Experiments were designed to analyze the effects of endothelium-derived relaxing factor(s) (EDRF; released basally or on stimulation with acetylcholine) and nitric oxide (NO) on smooth muscle of coronary arteries of different diameter. During contractions of the bioassay ring evoked with prostaglandin F(2α), the relaxations caused by basal EDRF were greater in the distal than in the proximal coronary arteries, whereas there was no difference in response to the EDRF released by acetylcholine. During direct superfusion, NO caused similar relaxations in proximal and distal coronary artery rings. Optimal tension, prostaglandin F(2α)-induced contractions, and relaxations caused by sodium nitroprusside were comparable in both preparations. In rings of proximal and distal coronary artery studied in organ chambers, acetylcholine caused comparable endothelium-dependent, whereas sodium nitroprusside and NO cause comparable endothelium-independent relaxations. These experiments indicate a difference in response of different-sized coronary arteries to basally released EDRF and suggest that the basally released factor differs from NO.link_to_subscribed_fulltex

Canine arteries release two different endothelium-derived relaxing factors

Experiments were designed to analyze the effects of ouabain on the response of vascular smooth muscle to endothelium-derived relaxing factors released under basal conditions and on stimulation with acetylcholine or bradykinin. Bioassay rings of canine coronary artery (without endothelium) were superfused with perfusate from canine left circumflex coronary arteries with endothelium (donor arteries). During contractions of the bioassay ring evoked by prostaglandin F(2α), the relaxations caused by endothelium-derived relaxing factor(s), released under basal conditions or on exposure of the endothelial cells of the donor artery to maximally effective concentrations of acetylcholine, were reduced by incubation of the bioassay ring with ouabain. However, the relaxations evoked by infusion of bradykinin were not altered by incubation of the bioassay rings with ouabain. These experiments demonstrate the release of two endothelium-derived relaxing factors that can be distinguished using ouabain.link_to_subscribed_fulltex

Stereoselective effect of diltiazem on endothelium-dependent relaxations in canine femoral arteries

Experiments were designed to analyze potential interactions between voltage-dependent calcium channel blockers and endothelium-dependent vascular responses. Rings of canine femoral artery were suspended for isometric force recording in organ chambers and contracted with prostaglandin F(2α). Removal of the endothelium had no effect on relaxations induced by d-cis-diltiazem (active stereoisomer), verapamil or nimodipine. When rings with endothelium were first partially relaxed with acetylcholine or the calcium ionophore A23187 the concentration-relaxation curve to d-cis-diltiazem (but not to verapamil or nimodipine) was significantly shifted to the right. Partial relaxation of femoral arterial rings without endothelium by sodium nitroprusside had no effect on relaxations evoked by diltiazem. Pretreatment with diltiazem (10 -6 M) had no effect on endothelium-dependent relaxations to acetylcholine in femoral artery rings. D-cis-Diltiazem partially reversed the relaxation induced by acetylcholine in a bioassay system, in which a ring of canine coronary artery without endothelium was superfused by solution passing through a segment of femoral artery with endothelium. D-cis-Diltiazem relaxed the bioassay ring when infused downstream of the perfused femoral artery with, or upstream of a femoral artery without endothelium. The effect of diltiazem was stereoselective (the less active 1-cis-diltiazem had no effect). Verapamil did not reverse the relaxation induced by acetylcholine and did not affect the reversal induced by diltiazem. These findings indicate that diltiazem specifically antagonizes the production and/or the release of endothelium-derived relaxing factor(s) stimulated by acetylcholine or A23187 in canine femoral arteries. The mechanism involves either a specific benzothiazepine-dependent inhibition of calcium influx or an interference with some other calcium-dependent or independent process in endothelial cells.link_to_subscribed_fulltex

Pharmacology of pentoxifylline in isolated canine arteries and veins

Pentoxifylline possesses vasodilator properties, but little information is available on the mechanism of action explaining this vasodilator effect. The present experiments were designed to determine the effects of the compound on vascular smooth muscle, endothelium, and adrenergic nerves in rings of isolated canine blood vessels. Pentoxifylline did not affect basal tension in coronary and femoral arteries or in saphenous and mesenteric veins; it did not alter the rhythmic activity of the latter, but did not cause endothelium-independent relaxations of unstimulated basilar arteries. In coronary arteries and saphenous veins, but not femoral arteries contracted with prostaglandin F(2α), the compound caused relaxations which were not affected by propranolol or by removal of the endothelium. Pentoxifylline inhibited the endothelium-dependent contractions to the Ca2+-ionophore A23187 in the basilar artery. In saphenous veins (with endothelium), pentoxifylline did not inhibit responses to high K+, electrical stimulation of the adrenergic nerves, or exogenous norepinephrine (NE); it reduced contractions evoked by xylazine and hypoxia. In the basilar artery and the saphenous vein, the inhibitory effect of pentoxifylline was prevented by inhibitors of cyclooxygenase and thromboxane synthetase. These experiments suggest that the dilator properties of pentoxifylline in isolated canine blood vessels are primarily at the level of the vascular smooth muscle and may involve decreased production of, or reduced responsiveness to, endogenous thromboxanes.link_to_subscribed_fulltex

Broadly tunable, diode pumped Alexandrite laser

We present design and first performance data of a broadly tunable Alexandrite laser longitudinally pumped by a newly developed high brightness single emitter diode laser module in the red spectral range