nitroarginine and 8-(4-sulfophenyl)theophylline

Our knowledge of the effects of P2-receptor activation on renal vascular tone comes mostly from in vitro models. We aimed to characterise the pharmacology of ATP in the renal circulation in vivo.. In pentobarbitone anaesthetized rabbits, we examined total renal and medullary vascular responses to ATP (0.2 and 0.8 mg kg(-1)), beta, gamma-methylene ATP (beta, gamma-mATP, 7 and 170 microg kg(-1)), alpha, beta-mATP (0.2 and 2 microg kg(-1)) and adenosine (2 and 6 microg kg(-1)) using transit-time ultrasound and laser Doppler flowmetry, respectively. We also determined whether adenosine receptors, NO or prostanoids contribute to the actions of the purinoceptor agonists.. Renal arterial boluses of ATP, beta,gamma-mATP, and adenosine produced biphasic changes; ischaemia followed by hyperaemia, in total renal and medullary blood flow. alpha,beta-mATP induced only ischaemia. The adenosine receptor antagonist 8-(p-sulphophenyl)theophylline reduced the responses to adenosine and the hyperaemic responses to ATP and beta,gamma-mATP only. NO synthase inhibition (Nomega-nitro-L-arginine) did not significantly alter responses to the P2 receptor agonists. Subsequent cyclooxygenase inhibition (ibuprofen) reduced the ATP- and beta, gamma-mATP-induced increases in renal blood flow. All other responses remained unchanged.. In the rabbit kidney in vivo, alpha, beta-mATP sensitive receptors mediate vasoconstriction. beta,gamma-mATP and ATP induce vasodilation at least partly through adenosine receptors. ATP induced renal vasodilatation is independent of NO and partly dependent on prostanoids in the bulk of the kidney, but not in the vasculature controlling medullary blood flow.

Topics: Adenosine; Adenosine Triphosphate; Animals; Cyclooxygenase Inhibitors; Ibuprofen; Kidney; Kidney Cortex; Kidney Medulla; Laser-Doppler Flowmetry; Male; Nitric Oxide Synthase; Nitroarginine; Prostaglandins; Purinergic P1 Receptor Agonists; Purinergic P1 Receptor Antagonists; Purinergic P2 Receptor Agonists; Purinergic P2 Receptor Antagonists; Rabbits; Receptors, Purinergic P1; Receptors, Purinergic P2; Regional Blood Flow; Renal Circulation; Theophylline

We examined pial arteriolar reactivity to a partially endothelial nitric oxide synthase (eNOS)-dependent vasodilator ADP as a function of chronic estrogen status. The eNOS-dependent portion of the ADP response was ascertained by comparing ADP-induced pial arteriolar dilations before and after suffusion of a NOS inhibitor, N(omega)-nitro-L-arginine (L-NNA; 1 mM) in intact, ovariectomized (Ovx), and 17beta-estradiol (E2)-treated Ovx females. We also examined whether ovariectomy altered the participation of other factors in the ADP response. Those factors were the following: 1) the prostanoid indomethacin (Indo); 2) the Ca2+-dependent K+ (K(Ca)) channel, iberiotoxin (IbTX); 3) the ATP-regulated K+ (K(ATP)) channel glibenclamide (Glib); 4) the K(Ca)-regulating epoxygenase pathway miconazole (Mic); and 5) the adenosine receptor 8-sulfophenyltheophylline (8-SPT). In intact females, the eNOS-dependent (L-NNA sensitive) portion of the ADP response represented approximately 50% of the total. The ADP response was retained in the Ovx rats but L-NNA sensitivity disappeared. On E2 replacement, the initial pattern was restored. ADP reactivity was unaffected by Indo, Glib, Mic, and 8-SPT. IbTX was associated with 50-80% reductions in the response to ADP in the intact group that was nonadditive with L-NNA, and 60-100% reductions in the Ovx group. The present findings suggest that estrogen influences the mechanisms responsible for ADP-induced vasodilation. The continued sensitivity to IbTX in Ovx rats, despite the loss of a NO contribution, is suggestive of a conversion to a hyperpolarizing factor dependency in the absence of E2.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Antifungal Agents; Arterioles; Calcium; Cardiovascular Agents; Endothelium, Vascular; Estrogens; Female; Glyburide; Hypoglycemic Agents; Indomethacin; Miconazole; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitroarginine; Ovariectomy; Peptides; Pia Mater; Potassium Channels; Rats; Rats, Sprague-Dawley; Theophylline; Vasodilation

To investigate the mechanisms involved in hypoxic vasodilation using an in vitro setup.. Retinal arteries with and without retinal tissue were mounted on a wire myograph. The segments were contracted with prostaglandin (PG)F(2alpha) (30 microM) or 120 mM K(+). Hypoxia was induced by replacement of O(2) by N(2) in the gas used to bubble the Krebs-Ringer bicarbonate organ bath solution.. Hypoxia induced complete relaxation of preparations with adherent retinal tissue contracted with PGF(2alpha). Preparations without retinal tissue were not affected by the change in oxygenation. When the retinal arteries were contracted with 120 mM K(+), hypoxia no longer induced relaxation of the preparation with adherent retinal tissue. The presence of an NO-synthase inhibitor (L-NA, 0.1 mM), a cyclooxygenase inhibitor (indomethacin, 50 microM), or an adenosine receptor antagonist (8-sulfophenyltheophylline, 1 mM) did not affect hypoxic vasodilation. Excitatory amino acids and lactate had no or only a limited effect on the PGF(2alpha)-induced contraction and are therefore unlikely mediators of hypoxic vasodilation. HCl (10 mM) reduced the pH to 6.1 +/- 0.08 (n = 4) and induced a pronounced but transient relaxation of the retinal artery contracted with PGF(2alpha) or 120 mM K(+), whereas hypoxia induced relaxation of the retinal artery contracted with PGF(2alpha) only in the presence of adherent retinal tissue.. Adherent retinal tissue mediates the hypoxic vasodilatation of bovine retinal arteries in vitro. Neither NO, prostanoids, adenosine, excitatory amino acids lactate or changes in pH seem to be involved in this hypoxic response.

Topics: Animals; Cattle; Cyclooxygenase Inhibitors; Dinoprost; Electromyography; Eye Proteins; Hydrogen-Ion Concentration; Hypoxia; Indomethacin; Muscle Proteins; Muscle, Smooth, Vascular; Nitric Oxide Synthase; Nitroarginine; Purinergic P1 Receptor Antagonists; Retina; Retinal Artery; Theophylline; Vasodilation

To investigate the role of endothelium-derived nitric oxide (EDNO) and adenosine in functional myocardial hyperemia, we examined the effect of NG-nitro-L-arginine (L-NNA) and 8-p-sulfophenyltheophylline (8-SPT) on coronary vasodilation in response to increased myocardial oxygen consumption in pentobarbital sodium-anesthetized dogs. L-NNA significantly attenuated the increase in coronary conductance from 28 +/- 6 to 16 +/- 2% with atrial pacing, from 69 +/- 5 to 36 +/- 6% with isoproterenol, and from 25 +/- 6 to 9 +/- 4% with constriction of the aorta. 8-SPT given alone attenuated the increase in coronary conductance to the same extent as L-NNA. The combined administration of L-NNA and 8-SPT did not further change coronary conductance. These findings suggest that EDNO and adenosine play an important role in functional hyperemia. EDNO-induced functional hyperemia appears to be dependent on adenosine receptor activation.

Topics: Adenosine; Animals; Arginine; Coronary Circulation; Dogs; Female; Hemodynamics; Hyperemia; Male; Nitric Oxide; Nitroarginine; Theophylline; Vascular Resistance

Intrarenal infusion of adenosine induces transient renal vasoconstriction followed by sustained renal vasodilation. The purpose of this study was to elucidate the role of endothelium-derived relaxing factor (EDRF) in renal hemodynamic actions of adenosine in anesthetized dogs. Intrarenal arterial infusion (i.r.a.) of EDRF synthesis inhibitors, L-NG-monomethyl-arginine (160 micrograms/kg/min) and L-NG-nitro-arginine (80 micrograms/kg/min), attenuated acetylcholine-induced increases in renal blood flow and renal vascular resistance was increased. Renal vasoconstriction elicited by adenosine (100 nmol/min i.r.a.) was potentiated and the duration was prolonged by pretreatment with either EDRF synthesis inhibitor. Adenosine infusion significantly decreased glomerular filtration rate (GFR) by more than 30% in the presence of EDRF inhibitors, whereas GFR remained unchanged by adenosine in the absence of EDRF synthesis inhibitors. L-arginine (2 mg/kg/min i.r.a.) significantly reversed the potentiation of adenosine-induced renal vasoconstriction and adenosine-induced reduction in GFR elicited by pretreatment with EDRF synthesis inhibitors. On the other hand, the adenosine A2 selective agonist, CGS 21680C (0.37 nmol/kg/min i.r.a), elicited monophasic renal vasodilation and this effect on renal blood flow was unaffected by EDRF inhibitor. These results suggest that arginine-derived EDRF is involved in the renal vascular action of adenosine. In the present experimental setting, we obtained no evidence for the interaction between arginine-derived EDRF and CGS 21680C-activated A2 adenosine receptor in renal vascular beds.

Topics: Acetylcholine; Adenosine; Animals; Arginine; Dogs; Female; Hemodynamics; Kidney; Male; Nitric Oxide; Nitroarginine; omega-N-Methylarginine; Phenethylamines; Renal Circulation; Theophylline