Influence of prostaglandin E2, indomethacin, and reserpine on renal vascular responses to nerve stimulation, pressor and depressor hormones.

Abstract

The effects of prostaglandin E, (PGE 2), indomethacin, and reserpine were evaluated in the rabbit renal vascular bed in situ under conditions of controlled blood flow. Intrarenal infusion of PGE 2 , 0.03 and 0.3 fig/min, decreased responses to renal nerve stimulation, intra-arterial norepinephrine, and angiotensin. Responses to nerve stimulation were decreased to a greater extent than responses to norepinephrine. At lower concentrations the effects of PG£ 2 on pressor responses and on vascular resistance could be separated. Reserpine decreased the histochemical evidence of adrenergic innervation and reduced the response to renal nerve stimulation, enhanced the response to norepinephrine, and was without effect on the response to angiotensin. Indomethacin decreased depressor responses to arachidonic acid, produced a small increase in renal vascular resistance but did not enhance renal pressor responses. The increase in renal vascular resistance after indomethacin was not modified by reserpine pretreatment. Indomethacin enhanced the renal response to bradykinin. These data show that PGE 2 possesses the ability to modulate pressor responses in the kidney. However, experiments with indomethacin suggest that endogenous prostaglandins neither modulate pressor responses nor mediate the response of the renal vascular bed to bradykinin. In addition, these data suggest that the increase in renal resistance after indomethacin is not dependent on the adrenergic nervous system.

Effects of Arachidonic Acid in the Rabbit Pulmonary and Systemic Vascular Beds in vivo

“…While AA appears to affect the systemic vasculature in a more complex fashion, our observations agree with the findings of oth ers which indicate that AA decreases Psa in the anesthetized dog [11,12] and reduces P«* and renal vascular resistance in the anesthe tized rabbit [13]. Although the latter effects of AA were blocked by indometacin under condition of freely variable cardiac output [ 13], in the present study with constant car diac output, cyclo-oxygenase inhibition did not affect the depressor effects of AA in the systemic circulation.…”

“…Although the latter effects of AA were blocked by indometacin under condition of freely variable cardiac output [ 13], in the present study with constant car diac output, cyclo-oxygenase inhibition did not affect the depressor effects of AA in the systemic circulation. Further, the systemic depressor response to AA was only partially inhibited in the presence of a leukotriene receptor antagonist.…”

“…The endoperoxides are further converted to the classical prostaglandins: D2, E2 and F2 are formed by nonenzymatic reduction, throm boxane A2 by the enzyme thromboxane syn thetase [3] and prostacyclin by the enzyme prostacyclin synthetase [4], In the second pathway, peroxidation of AA by the enzyme lipo-oxygenase produces unstable hydroperoxyeicosatetraenoic acids (HPETEs), which are then reduced to hydroxy acids (HETEs). Although four different lipo-oxygenase en zymes have been identified, 5-, 11-, 12-, and 15-lipo-oxygenases, of special interest is the 5-lipo-oxygenase pathway which leads, via an unstable intermediate (leukotriene A2), to the formation of leukotriene B2, C4, D4 and E4 [5,6], Exogenous AA increases pulmonary vas cular resistance in both isolated and intact dog lung [7,8], intact cat lung [8], isolated perfused guinea pig lung [9] and isolated rab bit lung [10], Furthermore, AA has been reported to produce a systemic depressor re sponse in dogs [11,12] and anesthetized rab bit [ 13], The pressor effects of AA in isolated perfused rabbit lungs and systemic depressor effects in intact anesthetized rabbits have been reported to be antagonized by indometacin, suggesting that AA is metabolized via the cyclo-oxygenase pathway to form va soactive products which cause pulmonary vasoconstriction and systemic vasodilation [10,13],…”

The renal kallikrein-kinin system.

“…Blockade of prostaglandin synthesis by indomethacin partly prevents the vasodilatory action of kinins in isolated blood vessels (Messina et al, 1975) and the isolated perfused dog kidney , but not in the isolated cat or rabbit (Fink et al, 1977) kidneys. Indomethacin completely blocks the vasopressinresistant reduction in urinary osmolality caused by kinin infusion .…”

The importance of endogenous prostaglandins other than prostacyclin, for the modulation of contractility of some rabbit blood vessels

“…Similarly the vasoconstrictor responses of some vessels to agonists are not changed after inhibition of cyclooxygenase by non-steroidal anti-inflammatory drugs, e.g. the vascular bed of the rabbit kidney (Fink et al, 1977) and the rabbit hindlimb (Gottlieb etal., 1980).…”