Attenuation by arachidonic acid of the effect of vasoconstrictor stimuli in the canine kidney.

The effect of arachidonic acid on the renal vasoconstrictor response elicited by sympathetic nerve stimulation, norepinephrine and angiotensin II in pentobarbital-anesthetized dogs, with and without pretreatment with the cyclooxygenase inhibitors, sodium meclofenamate or indomethacin was investigated. Stimulation of renal nerves at 2 to 8 Hz or injections into the renal artery of either norepinephrine or angiotensin II (0.06-0.5 micrograms) produced vasoconstriction and decreased blood flow to the kidney in frequency- and dose-related manners, respectively. In animals that were untreated with the cyclooxygenase inhibitors, renal arterial infusion of arachidonic acid at 15 micrograms kg-1 min-1 increased blood flow to the kidney and attenuated the vasoconstrictor effect of renal nerve stimulation, injected norepinephrine and angiotensin II. However, in dogs pretreated with either sodium meclofenamate or indomethacin (5 mg/kg), infusion of arachidonic acid failed to alter the renal blood flow and the vasoconstrictor response elicited by both adrenergic stimuli and by angiotensin II. In contrast, pretreatment of animals with the cyclooxygenase inhibitor, sodium meclofenamate, did not prevent either prostaglandin E2 or prostacyclin (4 ng kg-1 min-1) from increasing renal blood flow and inhibiting the renal vasoconstrictor response produced by either adrenergic stimuli or by angiotensin II. These data suggest that arachidonic acid produces renal vasodilation and attenuates the vasoconstrictor effect of the adrenergic stimuli and angiotensin II through its transformation by cyclooxygenase into one or more produced, presumably prostaglandin E2 and/or prostacyclin.

Prostacyclin and prostaglandin E2 effects on adrenergic transmission in the kidney of anesthetized dog.

The effect of prostaglandin E2 (PGE2) and prostacyclin (PGI2) on the renal venous output of the adrenergic transmitter and on the renal vasoconstriction produced by sympathetic nerve stimulation and by norepinephrine was studied in pentobarbital-anesthetized dog. Renal arterial infusion of either PGE2 or PGI2 (4 ng kg-1 min-1) increased blood flow to the kidney and inhibited the vasoconstrictor response elicited by renal nerve stimulation (1-8 Hz) and by renal arterial injections of norepinephrine (0.006-0.5 microgram). However, during infusion of either PGE2 or PGI2, the renal venous output of norepinephrine caused by nerve stimulation was not altered. In contrast, substance P (2 ng kg-1 min-1), which also increased the blood flow to the kidney, did not affect the renal vasoconstrictor response elicited by either adrenergic stimulus. These results suggest that PGE2 and PGI2 reduce the vasoconstrictor effect of sympathetic nerve stimulation in the canine kidney by acting on the vascular smooth muscle.

Bradykinin effects on adrenergic transmission in the canine kidney: relation to prostaglandins.

We studied the action(s) of bradykinin at the renal vascular neuroeffector junction, and its relation to prostaglandin synthesis, by investigating the effect of the peptide on the renal venous output of the neurotransmitter and on the renal vasoconstrictor responses elicited by sympathetic nerve stimulation and by norepinephrine in pentobarbital-anesthetized dogs. Renal arterial infusion of bradykinin at 10 ng . kg-1 . min-1 increased blood flow to the kidney and inhibited the vasoconstrictor effect of renal nerve stimulation (1-8 Hz) and injected norepinephrine (0.06-0.5 micrograms). However, bradykinin did not alter the rise in venous output of norepinephrine elicited by nerve stimulation. Infusion of another vasodilatory peptide, substance P (2 ng . kg-1 . min-1) into the renal artery also increased blood flow to the kidney but failed to alter the vasoconstriction produced by either adrenergic stimulus. Pretreatment of dogs with an inhibitor of prostaglandin synthesis, either sodium meclofenamate or indomethacin (5 mg/kg), abolished the inhibitory effect of the kinin on renal vasoconstriction produced by adrenergic stimuli. These data suggest that bradykinin acts on postjunctional sites to reduce adrenergically induced vasoconstriction in the canine kidney by a mechanism dependent on prostaglandin synthesis.

Inhibition by bradykinin of the vascular action of angiotensin II in the dog kidney.

In the dog anesthetized with pentobarbital, the effect of bradykinin on the lowering of renal blood flow produced by bolus injections of angiotensin II was studied. Injection into the renal artery of angiotensin II (0.06--0.50 microgram) caused vasoconstriction and decreased blood flow to the kidney in a dose-related manner. Renal arterial infusion of bradykinin (10 ng kg-1 min-1), prostaglandin (PG) E2 (4 ng kg-1 min-1) or PGI2 (4 ng kg-1 min-1) produced renal vasodilation and inhibited the vasoconstrictor effect of angiotensin II. However, renal arterial infusion of another vasodilatory peptide, substance P (2 ng kg-1 min-1), did not alter the effect of angiotensin II on the renal vasculature. Pretreatment of dogs with an inhibitor of PG synthesis, sodium meclofenamate (5 mg/kg), abolished the inhibitory effect of bradykinin on angiotensin II-induced renal vasoconstriction. In contrast, renal arterial infusion of either PGE2 or PGI2 was equally effective in reducing the renal vascular effect of angiotensin II in animals with and without meclofenamate pretreatment. These results suggest that bradykinin reduces the reactivity of the renal vasculature to angiotensin II by a mechanism dependent upon PG synthesis.

Inhibition of bradykinin of the vascular effects of pressor hormones in the canine kidney: relationship to prostaglandins.

1. Renal arterial injection of bolus doses of angiotensin II or noradrenaline, (0.06, 0.12 and 0.25 microgram) caused renal vasoconstriction and decreased blood flow to the kidney in a dose-related manner in dogs anaesthetized by sodium pentobarbital. 2. The effect of angiotensin II and noradrenaline in lowering renal blood flow was reduced during renal arterial infusion of either bradykinin (10 ng min-1 kg-1) or prostaglandin E2 (4 ng min-1 kg-1). 3. Pretreatment of the dogs with an inhibitor of prostaglandin synthesis, sodium meclofenamate (5 mg/kg), blunted the inhibitory action of bradykinin, but not that of prostaglandin E2, on renal vascular reactivity to angiotensin II and noradrenaline. 4. These results indicate that bradykinin reduces the renal vasoconstriction induced by angiotensin II and noradrenaline in the dog by a mechanism dependent upon synthesis of prostaglandins.

Modulation of adrenergic neuroeffector events in the renal vasculature: role of prostaglandins.

The major products of arachidonic acid metabolism in the kidney (PGE2, PGI2, PGF2 alpha) influence adrenergic neuroeffector events. PGE2 and PGI2 inhibit the vasoconstrictor responses elicited by sympathetic nerve stimulation and by injected norepinephrine in the rabbit and dog kidney. PGE2 also reduces release of the adrenergic transmitter from the rabbit kidney. In contrast, PGF2 alpha enhances adrenergically induced vasoconstriction. In the rabbit kidney, release of the adrenergic transmitter and the vasoconstrictor responses to nerve stimulation and to injected norepinephrine are enhanced by blockade of prostaglandin synthesis, and are reduced during stimulation of prostaglandin synthesis by either arachidonic acid or bradykinin. In contrast, in the rat kidney, adrenergically induced vasoconstriction is enhanced by PGE2, PGI2, and arachidonic acid and is reduced by prostaglandin synthesis inhibitors. This suggests major species differences in the modulatory action of prostaglandins at the adrenergic neuroeffector junction. This difference between rat and other species could be due to difference in prostaglandin receptors or in the events resulting from the interaction of prostaglandins with the receptors at the adrenergic neuroeffector junction.