Participation of the Prostaglandins in the Control of Renal Blood Flow during Acute Reduction of Cardiac Output in the Dog

Oliver, Juan A.; Sciacca, Robert R.; Pinto, John T.; Cannon, Paul J.

doi:10.1172/jci110018

Cited by 114 publications

(27 citation statements)

References 36 publications

(52 reference statements)

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“…The fact that acute and chronic hypercalcemia cause a decreased RBF and GFR in both man and experimental animals has been repeatedly reported (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 94%

Control of Renal Hemodynamics and Glomerular Filtration Rate in Chronic Hypercalcemia

Levi¹,

Ellis²,

Berl³

1983

J. Clin. Invest.

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A B S T R A C T The role of prostaglandins (PG), reninangiotensin system (RAS) and calcium (Ca) in the control of renal hemodynamics and glomerular filtration rate (GFR) in chronic hypercalcemia (serum Ca 12.8 mg%) was studied. Renal blood flow (RBF, 6.39 ml/ min per gram kidney weight [gkw]) and GFR (0.52 ml/min per gkw) were significantly decreased in hypercalcemic rats when compared with normocalcemic rats (7.15, P < 0.001 and 0.74, P < 0.05, respectively). These changes in RBF and GFR occurred independent of any significant alterations in systemic hemodynamics, blood and plasma volume. Inhibition of the renal PG with indomethacin resulted in marked decrements in both RBF (6.39-4.12 ml/min per gkw, P < 0.01) and GFR (0.52-0.19 ml/min per gkw, P < 0.01) in hypercalcemic rats, whereas there was no significant alterations in normocalcemic rats. Inhibition of the RAS with captopril resulted in marked increments in both RBF (6.39-7.35 ml/min per gkw, P < 0.05) and GFR (0.52-0.74 ml/min per gkw, P < 0.05) in hypercalcemic rats. In fact, there was no significant difference from the RBF and GFR of similarly treated normocalcemic rats. Similar results were also obtained with the competitive angiotensin II (AII) antagonist (sarcosyll-isoleucyl5-glycyl8) AII. Since both the renal PG and the RAS are involved in the control of RBF and GFR in hypercalcemia, the role of each is best revealed in the absence of the other. Hence, comparison of the RBF and GFR in the PG-inhibited hypercalcemic rats in the presence of AII (4.12 and 0.19 ml/ min per gkw, respectively) and absence of AII (5.99 and 0.53 ml/min per gkw, P < 0.01 for both) reveals the vasoconstrictive role for All in hypercalcemia. On the other hand, comparison of the RBF and GFR in the AII-inhibited hypercalcemic rats in the presence of PG (7.35 and 0.74 ml/min per gkw, respectively) and absence of PG (5.99 and 0.53 ml/min per gkw, P < 0.01 and P < 0.05, respectively) reveals the vasodilatory role for PG in hypercalcemia. Finally, comparison of the RBF and GFR in both PG-and Allinhibited hypercalcemic rats (5.99 and 0.53 ml/min per gkw, respectively) with similarly treated normocalcemic rats (7.30 and 0.94 ml/min per gkw, P < 0.001 and P < 0.005, respectively) reveals the vasoconstrictive role for Ca in chronic hypercalcemia. Our study therefore demonstrates that in chronic hypercalcemia the RBF and GFR are controlled by an active interplay of the vasoconstrictive effect of AII, the vasodilatory effect of renal PG, and the direct vasoconstrictive effect of Ca, independent of either AII or PG. The sum total of these forces produces a modest but significant decrease in RBF and GFR. INTRODUCTIONThe association of acute and chronic hypercalcemia with decrements in renal blood flow (RBF)' and glomerular filtration rate (GFR) has been widely recognized in both man and experimental animals (1-15). While the mechanisms responsible for the decrement in RBF and GFR have been studied in anesthetized, acutely hypercalcemic animals, there have been no such studies in the setting...

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Section: Discussionmentioning

confidence: 94%

Control of Renal Hemodynamics and Glomerular Filtration Rate in Chronic Hypercalcemia

Levi¹,

Ellis²,

Berl³

1983

J. Clin. Invest.

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“…It is well known that cyclo-oxygenase inhibitors have little or no effect on normal RBF, but do reduce RBF when the renal circulation is compromised (Oliver et al, 1981;Stoff & Clive, 1983). Thus, endogenous release of cyclo-oxygenase products is a reserve mechanism, not increasing normal RBF but helping to maintain a damaged circulation.…”

Section: Discussionmentioning

confidence: 99%

Support of renal blood flow after ischaemic‐reperfusion injury by endogenous formation of nitric oxide and of cyclo‐oxygenase vasodilator metabolites

Cristol

Thiemermann

Mitchell

et al. 1993

British J Pharmacology

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1 Ischaemia-reperfusion injury in the kidney is associated with a loss of autoregulation, an increase in renal vascular resistance (RVR), a decrease of renal blood flow (RBF) and ultimately acute renal failure. The aim of this study was to investigate the role of the release of endogenous nitric oxide (NO) in the recovery of RBF after ischaemic injury of the renal vascular bed.2 Anaesthetized rats (thiopentone sodium; 120 mg kg-', i.p.) were submitted to acute renal ischaemia followed by 2 or 6 h of reperfusion (I/R). Reperfusion was associated with a significant reduction in RBF, an increase in RVR, and an impairment of the vasodilator effect of acetylcholine (ACh).3 N0-nitro-L-arginine methyl ester (L-NAME, 30 iLg kg-' min-, i.v., n = 5) significantly prevented the recovery of RBF after I/R injury. Similarly, inhibition of prostanoid formation with indomethacin (5 mg kg-', i.v., n = 4) significantly enhanced the rise in RVR associated with I/R injury. 4 Infusion of L-arginine (L-Arg; I or 3 mg kg-' min 1, i.v., n = 5 and 4, respectively) or D-Arg (1 mg kg-' min', i.v., n = 6), starting 30 min after occlusion, did not improve the recovery of RBF. Furthermore, infusion of L-Arg (20 mg kg-' min-' for 15 min; n = 4) had no effect on the I/R-induced impairment of the vasodilator responses to ACh. 5 To elucidate the relative importance of the constitutive and inducible NO synthase isoforms for the formation of NO after I/R, calcium-dependent (constitutive) and calcium-independent (inducible) NO synthase activities were measured in kidney homogenates obtained from ischaemic or non-ischaemic kidneys. A calcium-independent NO synthase activity was not detectable in kidney homogenates obtained from either sham-operated control rats or from animals subjected to I/R. Moreover, dexamethasone (3 mg kg-', i.v., 60 min prior to I/R, n = 6), an inhibitor of the induction of NO synthase, had no effect on either RBF or RVR in rats subjected to I/R. In contrast to I/R, lipopolysaccaride (LPS, endotoxin; 5 mg kg-', i.p., n = 3) caused a significant induction of a calcium-independent NO synthase activity in the kidney. 6 These results confirm the importance of the release of vasodilator cyclo-oxygenase metabolites in the compromised renal circulation and indicate that the formation of NO derived from the constitutive, but not the inducible NO synthase, is also important for the maintenance of RBF after I/R injury of the renal vascular bed.

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“…The relationship between endotoxin and prostaglandins was also examined in the kidney where an interplay of vasoconstrictor and vasodilator factors dictate kidney function, particularly during systemic hypotension and high sympathetic activity (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The decrease in MAP in prostaglandin intact group I dogs was associated with a decrease in GFR but not RBF in both innervated and denervated kidneys.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental maneuvers that cause renal ischemia (e.g., renal nerve stimulation, angiotensin or catecholamine infusion, hemorrhage, sodium depletion, heart failure, cirrhosis, and hypercapnia) cause enhanced renal vasoconstriction when prostaglandin synthesis is inhibited (8,(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). In addition, each of these vasoconstrictive stimuli markedly stimulates renal prostaglandin synthesis that leads to renal vasodilatation and opposes the vasoconstrictor input (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Hence, the renal vasodilatory system mediated by intrarenal production of prostaglandins attenuates renal ischemia in the setting of an unstable systemic circulation; conversely, prostaglandin synthesis inhibition enhances renal ischemia because vasoconstrictive stimuli are unopposed by compensatory vasodilatation.…”

Section: Introductionmentioning

confidence: 99%

Dissociation of systemic and renal effects in endotoxemia. Prostaglandin inhibition uncovers an important role of renal nerves.

Henrich¹,

Hamasaki²,

Said³

et al. 1982

J. Clin. Invest.

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A B S T R A C T To elucidate the mechanisms responsible for systemic and renal hemodynamic changes in early endotoxemia, the roles of prostaglandins (PG) and renal nerves were investigated. Endotoxin (E, 3 ag/kg i.v.) was given to two groups of anesthetized dogs that had undergone unilateral renal denervation: Group I (n = 9) E only; Group II (n = 11) E + indomethacin (10 mg/kg i.v.) or meclofenamate (5 mg/kg i.v.). A third group of dogs (Group III, n = 5) received indomethacin (10 mg/kg i.v.) only. 1 h after E in group I dogs, mean arterial pressure (MAP) decreased from 126 to 94 mm Hg (P < 0.001), and prostacyclin (6-keto-Fla metabolite, PGI2) increased (from 0.64 to 2.08 ng/ml, P < 0.005). Glomerular filtration rate (GFR) and renal blood flow (RBF) declined comparably both in innervated and denervated kidneys. In marked contrast, group II dogs had a stable MAP (136-144 mm Hg, NS) and no increase in PGI2 levels. Plasma renin activity (0.7-2.5 ng/ml per h, P < 0.005) increased, and renin secretion was greater in innervated compared with denervated kidneys (255 vs. 74 U/min, P < 0.01) in these PG-inhibited dogs. In addition, denervated kidneys in group II dogs had a greater GFR (42 vs. 34 ml/min, P < 0.01) and RBF (241 vs. 182 ml/min, P < 0.01) than innervated kid- renin activity or PGI2 during the study. These results suggest that PGI2 mediates the systemic hypotension of early endotoxemia in the PG-intact animal. Moreover, PG inhibition uncovers an important effect of E to increase efferent renal nerve activity with a consequent decline in GFR and RBF independent of changes in MAP. Finally, the results demonstrate that renal nerves are important stimuli to renin secretion in early endotoxemia via pathways that are PG-independent.

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Participation of the Prostaglandins in the Control of Renal Blood Flow during Acute Reduction of Cardiac Output in the Dog

Cited by 114 publications

References 36 publications

Control of Renal Hemodynamics and Glomerular Filtration Rate in Chronic Hypercalcemia

Control of Renal Hemodynamics and Glomerular Filtration Rate in Chronic Hypercalcemia

Support of renal blood flow after ischaemic‐reperfusion injury by endogenous formation of nitric oxide and of cyclo‐oxygenase vasodilator metabolites

Dissociation of systemic and renal effects in endotoxemia. Prostaglandin inhibition uncovers an important role of renal nerves.

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