Influence of renal denervation on vascular responsiveness of isolated rat intrarenal arteries

Abstract

Microsurgical renal denervation of the rat has been reported to increase blood loss and bleeding time after a standardized kidney resection. To investigate the vascular effects of denervation, isolated intrarenal arteries were studied using sensitive 'isometric' recording equipment. Four pieces of evidence were obtained to indicate an effective functional denervation I week after renal nerve transection: (i) Phentolamine reduced the K+-induced contraction in controls but not in denervated arteries. (ii) The K+-induced contraction was significantly smaller in denervated than in control arteries. (iii) Noradrenaline (NA) was a significantly more potent vasoconstrictor (4 x) in denervated than in control arteries. (iv) Cocaine increased the NA sensitivity in control arteries (3 x), whereas it failed to do so in denervated vessels. Vasopressin, 5-hydroxytryptamine (5-HT), NA (in the presence of cocaine), prostaglandin F2 alpha (PGF2 alpha) and dopamine (DA) produced concentration-dependent contractions in the mentioned order of potency. Denervated arteries were found to be about two to three times more sensitive to the vasoconstrictors than control arteries. Angiotensin I and II had no contractile effect in any of the vessel segments examined. Indomethacin-pretreated arteries also failed to respond to angiotensin II. Neuropeptide Y produced only weak contractions and failed to influence the NA concentration-response relationship in either control or denervated arteries. In conclusion, renal denervation caused a general supersensitivity of the vascular smooth muscle cells to both circulating and non-circulating vasoconstrictors. Our results cannot explain the increased blood loss and bleeding time seen after denervation, but rather support the view that the enhanced bleeding was caused by an interrupted vasoconstrictor influence of the sympathetic nerves.

Impact of renal transplantation on small vessel reactivity1

“…In rat interlobar arteries, Ang I and II were reported to have no contractile effects approximately 1 week after renal denervation (13). Eighteen weeks after denervation, we found constrictor responses to Ang II of similar intensity in small vessels isolated from denervated and native kidneys.…”

“…The present study reveals that, 18 weeks after denervation of single kidneys, the responses of small renal vessels to AVP is not elevated compared with resistance vessels from native single kidneys or vessels from kidneys of rats that did not undergo any surgery. However, 1 week after denervation, responsiveness of renal interlobular arteries to AVP has been reported to be increased (13). Plasma concentrations of Ang II and AVP levels are elevated in patients with chronic renal failure.…”

“…Vascular supersensitivity to NE, which can be explained in part by the loss of neuronal uptake sites, has been found early after renal denervation (13,14). There is evidence for increased ␣ receptor sensitivity to NE in renal transplant recipients (15).…”

Effects of renal denervation on renal pelvic contractions and connexin expression in rats

“…) and others (Hogestatt et al . ) showing that systemic sympathectomy or topical renal denervation elicited supersensitivity to adrenergic stimulation in intrarenal arteries. Together, these findings suggest that renal pelvic and vascular smooth muscle differ from each other with respect to the consequences of chronic removal of sympathetic tone on agonist‐induced contractile responses.…”

“…As it has been shown that the denervation‐induced supersensitivity of vascular smooth muscle extends beyond adrenergic stimulation to also affect non‐adrenergic stimuli (Hogestatt et al . , Grisk et al . ), we opted to investigate the responses of renal pelves from transplanted and non‐transplanted solitary kidneys to ET‐1.…”