The Role of Renal Nerves and Prostaglandins in Control of Renal Hemodynamics and Plasma Renin Activity during Hypotensive Hemorrhage in the Dog

Abstract

A B S T R A C T The effects of hypotensive hemorrhage (HH) on renal hemodynamics and plasma renin activity (PRA) during prostaglandin (PG) synthesis inhibition were examined in three groups ofdogs. In each group of animals arterial blood pressure was lowered by a 30% decrement. In the first group of eight control animals, HH was not associated with a significant change in glomerular filtration rate (GFR, 42-36 ml/min, NS); renal blood flow (RBF) declined significantly, from 234 to 171 ml/min, P < 0.05. In the second group of eight animals, pretreated with RO 20-5720 (RO, 2 mg/kg), a competitive inhibitor of PG synthesis, HH was associated with a significant fall in GFR (43-17 ml/min, P < 0.001) and RBF (195-89 ml/min, P < 0.001). In the third group of eight animals, pretreatment with indomethacin (IN, 10 mg/kg), a chemically dissimilar PG inhibitor, HH was also associated with a significant fall in GFR (38-8 ml/min, P < 0.001) and RBF (150-30 ml/min, P < 0.001). Renal denervation attenuated this renal ischemic effect of HH in the presence of PG inhibition. In the RO group, GFR (34 vs. 17 ml/min, P < 0.005) and RBF (145 vs. 89 ml/min, P < 0.025) were significantly greater in denervated vs. innervated kidneys during HH. Similarly, in animals treated with IN, a significantly higher GFR (28 vs. 8 ml/min, P < 0.005) and RBF (101 vs. 30 ml/min, P < 0.005) occurred in denervated as compared to innervated kid- neys during HH. With HH, the increase in PRA in the control group (3.34-11.68 ng/ml per h, P < 0.005) was no different than that observed in the RO group (4.96-18.9 ng/ml per h, P < 0.001) or IN group (4.71-17.8 ng/ml per h, P < 0.001). In summary, the present results indicate that renal PG significantly attenuate the effect of HH to decrease GFR and RBF. Furthermore, renal denervation exerts a protective effect against the enhanced renal ischemic effects which occur in the presence of PG inhibition during HH. Finally, PG inhibition does not alter the effect of HH to cause anl increase in PRA.

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

“…This finding is in agreement with other studies in which inhibition of prostaglandins reduced renal blood flow but had no effect on glomerular filtration rate (28); however, it contrasts with the observations that prostaglandin blockade significantly reduced the glomerular filtration rate in dogs with hypotensive hemorrhage (14,31) and in patients with Bartter's syndrome (42), with the nephrotic syndrome (43), and with cirrhosis with ascitis (16).…”

“…Renal prostaglandin synthesis is increased in sodium depletion (30), hemorrhagic hypotension (31), renal artery constriction (31), and cirrhosis with ascitis (33). In all these conditions, administration of inhibitors of prostaglandin synthesis reduces renal blood flow (12,15,16,31). The mechanism(s) whereby the prostaglandins attenuate renal vasoconstrictor mechanisms remains to be determined.…”

Protective effect of renal denervation on normotensive endotoxemia-induced acute renal failure in mice

“…In a dog model of sepsis, the role of renal nerves was also demonstrated after prostacyclin inhibition (5), suggesting an interaction between prostaglandins and renal nerve stimulation. In that regard, it is known that both angiotensin and increased renal nerve activity stimulate vasodilating prostaglandins (PGI 2 and PGE 2 ) in the kidney (4). Previous studies have shown an upregulation of NO synthase activity with ␣-adrenergic activity (15,17).…”

Hormonal Disturbances in Visceral Leishmaniasis (Kala-Azar)

“…31,32 The systemic inflammatory state and the presence of interstitial nephritis act as important sources of prostaglandin and nitric oxide secretions, resulting in arterial hypotension, increased medullary blood flow, elevated interstitial pressure, and decreased renal tubular reabsorption of sodium, potassium, calcium, and magnesium in these patients. 33,34 Characteristics of primary thyroid insufficiency were observed in patients with high TSH, and low T 3 and free-T 4 plasmatic concentrations. Evidences of primary pituitary hypofunction and secondary hypothyroidism were observed in patients with low TSH and low free-T 4 plasma levels.…”