Angiotensin and thromboxane in the enhanced renal adrenergic nerve sensitivity of acute renal failure.
The roles of intrarenal angiotensin (A) and thromboxane (TX) in the vascular hypersensitivity to renal nerve stimulation (RNS) and paradoxical vasoconstriction to renal perfusion pressure (RPP) reduction in the autoregulatory range in 1 wk norepinephrine (NE)-induced acute renal failure (ARF) in rats were investigated. Renal blood flow (RBF) responses were determined before and during intrarenal infusion of an AII and TXA2 antagonist. Saralasin or SQ29548 alone partially corrected the slopes of RBF to RNS and RPP reduction in NE-ARF rats (P less than 0.02). Saralasin + SQ29548 normalized the RBF response to RNS. While combined saralasin + SQ29548 eliminated the vasoconstriction to RPP reduction, similar to the effect of renal denervation, appropriate vasodilatation was not restored. Renal vein norepinephrine efflux during RNS was disproportionately increased in NE-ARF (P less than 0.001) and was suppressed by saralasin + SQ29548 infusion (P less than 0.005). It is concluded that the enhanced sensitivity to RNS and paradoxical vasoconstriction to RPP reduction in 1 wk NE-ARF kidneys are the result of intrarenal TX and AII acceleration of neurotransmitter release to adrenergic nerve activity.
Robinette
J B
JB
Department of Medicine, University of Colorado Health Science Center, Denver.
Conger
J D
JD
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001783:Blood Flow Velocity; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000294:innervation; D009638:Norepinephrine / Q000097:blood / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation; D012504:Saralasin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D000804:Angiotensin II; D013928:Thromboxane A2; C045749:SQ 29548; D012504:Saralasin; D009638:Norepinephrine