Mechanisms involved in the activation of ischemically sensitive, afferent renal nerve mediated reflex increases in hind-limb vascular resistance in the anesthetized rabbit.
Acute occlusion of the renal circulation in the anesthetized rabbit results in a neurally mediated, reflex increase in hind-limb vascular resistance, which is flow rather than pressure dependent. This suggests that the activating stimulus could be ischemia. In the present study vascularly isolated kidneys were perfused with hypoxemic or hypercapnic blood, and the hind-limb vascular response was measured. Renal perfusion with hypoxemic blood resulted in an increase in femoral perfusion pressure (FPP), which was negatively correlated with the oxygen tension of the blood. At a PO2 of 36.4 +/- 0.9 mmHg (1 mmHg = 133.3 Pa), FPP rose by 34.4 +/- 5.7 mmHg. Renal denervation abolished this effect. Renal perfusion with hypercapnic blood had no effect on FPP. Prostaglandin E2, bradykinin, and adenosine are released during renal ischemia and have been implicated in the mediation of afferent renal nerve activity; intrarenal administration (prostaglandin E2, 10 micrograms; bradykinin, 5 micrograms; adenosine, 20 micrograms; as a 1-mL bolus) during renal perfusion with normoxemic blood elicited increases in FPP of 32.4 +/- 13.2, 19.2 +/- 3.7, and 55.6 +/- 17.8 mmHg, respectively. Intrarenal indomethacin, aprotonin, and aminophylline all inhibited the increase in FPP observed during renal perfusion with hypoxemic blood. These data indicate that renal hypoxemia stimulates an afferent renal nerve mediated increase in FPP and suggest that prostaglandin E2, bradykinin, and adenosine may all be involved in the activation of ischemically sensitive R1 chemoreceptors.
Ashton
N
N
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Clarke
C G
CG
Eddy
D E
DE
Swift
F V
FV
D000241:Adenosine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D006614:Hindlimb / Q000098:blood supply*; D006935:Hypercapnia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D011453:Prostaglandins / Q000494:pharmacology; D011817:Rabbits; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D011453:Prostaglandins; D000241:Adenosine; D001920:Bradykinin