Angiotensin and thromboxane in the enhanced renal adrenergic nerve sensitivity of acute renal failure.

Abstract

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 < 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 < 0.001) and was suppressed by saralasin + SQ29548 infusion (P < 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. (J. Clin. Invest. 1990Invest. . 86:1532Invest. -1539

Analytical construct of reversible desensitization of pituitary-testicular signaling: illustrative application in aging

“…4) According to such analyses, older age is associated with diminished LH efficacy and, apparently, heightened T sensitivity and LH potency. The last two preliminary findings could be consistent with the broader concept of target organ denervation hypersensitivity, which is recognized in neuronal, vascular, renal, muscular, and other adaptive physiological systems (15,22,38,41,44,49,50). A relative LHdeficiency state was inferred here in older men by their lower mass of LH secreted per burst ( Fig.…”

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

“…The vascular hypersensitivity to renal nerve stimulation and paradoxical vasoconstriction to renal perfusion pressure reduction was observed in a model of norepi-nephrine-induced acute renal failure in rats (Robinette and Conger, 1990). Blocking studies by saralasin showed that they are the result of intrarenal Ang II acceleration of neurotransmitter release to adrenergic nerve activity.…”

Neuroendocrine stress response: implications for cardiac surgery-associated acute kidney injury

“…The inappropriate renal vasoconstriction mediated by SNS and RAAS stimulation adds to the presence of leukotrienes, thromboxanes and endothelin causing an exaggerated vasoconstrictive renal vascular response [32][33][34]. Additionally, the renal vascular endothelium is over-sensitized to vasoconstrictors and poorly responsive to vasodilators due to the excessive availability of intracellular calcium [34].…”

“…The mechanism of initial renal endothelial damage is ischemia-reperfusion [20,23]. Endothelial injury causes renal autoregulation loss, sensitivity to vasoconstrictors, and blunted response to nitric oxide with further renal perfusion impairment and tubular injury [32][33][34]. Cortico-medullary junction and outer medulla nephrons are the most susceptible [20,22,23].…”