Mechanisms involved in the activation of ischemically sensitive, afferent renal nerve mediated reflex increases in hind-limb vascular resistance in the anesthetized rabbit

Abstract

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.

Short-term effects of catheter-based renal denervation on cardiac sympathetic drive and cardiac baroreflex function in heart failure

“…Although the role of the renal afferents has been studied in the development of hypertension [38,39], there have been few studies that have looked at their role in HF [40,41]. This is surprising as the pathology of HF is associated with changes that would be expected to alter afferent renal nerve activity, including increased venous pressure, decreased renal perfusion pressure and blood flow, altered nitric oxide production and increased angiotensin II and endothelin levels [40][41][42][43][44]. In HF, the interaction of these factors with the afferent renal reflex may be more complex; for example, studies in anaesthetised rats indicate that the renal mechanosensory reflex is blunted in HF due to actions of high circulating levels of angiotensin II and endothelin-1 [40,41].…”

Cooperative Oxygen Sensing by the Kidney and Carotid Body in Blood Pressure Control

“…However, whether there is a threshold, or graded thresholds of renal tissue partial oxygen pressure for renal afferent nerve activation is unknown. Furthermore, performing the same experiment using normoxic blood and ischemic metabolites such as bradykinin, prostaglandin E2, and adenosine elicits similar rises in blood pressure (Ashton et al, 1994 ). This demonstrates that both low partial pressure of oxygen and ischemic metabolites can directly and/or indirectly stimulate renal sensory nerve fibers, promoting reflex increase of the sympathetic nerve activity, and blood pressure (Katholi et al, 1985 ).…”

“…Indeed, perfusion of the kidney with hypoxic blood (PaO 2 : 36 mmHg) is enough to increase femoral perfusion pressure by >30 mmHg. This response is mediated by renal afferent nerves as it was abolished after denervating the kidney (Ashton et al, 1994 ). However, whether there is a threshold, or graded thresholds of renal tissue partial oxygen pressure for renal afferent nerve activation is unknown.…”

The role of the renal afferent and efferent nerve fibers in heart failure

“…A decrease in renal perfusion by balloon inflation in the aorta for 2 min (which is likely to activate chemo- and inhibit mechanoreceptors) caused an increase in hindlimb vascular resistance in anesthetized rabbits (Rankin et al, 1992 ). The decreased renal perfusion is thought to elicit hypoxic-driven release of local mediators, such prostaglandin E2, bradykinin, and adenosine, which stimulate renal afferents leading to neutrally-mediated increases in hindlimb vascular resistance (Ashton et al, 1994 ). The main responses to renal mechanoreceptor activation are abolished by spinal cord transection at T6, indicating that the mechanoreceptor reno-renal reflex is dependent on central integration (Francisco et al, 1980 ; Kopp et al, 1985 ).…”