title: Sympathetic denervation facilitates L-type Ca2+ channel activation in renal but not in mesenteric resistance arteries.
abstract: OBJECTIVE
  Sympathetic denervation enhances agonist-induced vasoconstriction. This effect may involve altered function of signaling mechanisms such as Rho kinase (Rock) and L-type Ca channels downstream from vasoconstrictor receptors. We tested if enhanced Rock and L-type calcium channel activation contribute to exaggerated norepinephrine-induced vasoconstrictions in renal and mesenteric resistance arteries after sympathectomy.
  
  
  METHODS
  Rats underwent neonatal sympathectomy or sham sympathectomy. Resistance arteries were investigated by small vessel myography. Vascular Rock and L-type Ca channel expression as well as Rock activation were investigated by quantitative real-time PCR and Western blot. Vascular smooth muscle cell (VSMC) membrane potential was recorded with microelectrodes.
  
  
  RESULTS
  Sympathetic denervation enhanced norepinephrine sensitivity in renal and mesenteric arteries. Both, Rock inhibition or L-type Ca inhibition shifted the norepinephrine concentration-response curve to the right. This effect was more pronounced in renal than in mesenteric arteries from sympathectomized vs. sham-sympathectomized animals. The L-type Ca channel activator S-(-)-BayK8644 elicited strong vasoconstrictions only in renal arteries from sympathectomized rats. Rock activity and L-type Ca channel α-subunit expression were similar in renal arteries from sympathectomized and sham-sympathectomized animals. VSMC membrane potential was -57.5 ± 2.0 and -64.3 ± 0.3 mV (P < 0.01), respectively, in renal arteries from sympathectomized and from sham-sympathectomized rats. Depolarization enhanced and KATP channel activation abolished S-(-)-BayK8644-induced contractions in renal arteries from sympathectomized rats.
  
  
  CONCLUSIONS
  Sympathetic denervation enhances L-type Ca channel-dependent signaling in renal but not in mesenteric arteries. This effect may be partly explained by the decreased VSMC membrane potential in denervated renal arteries.
authors: aInstitute of Physiology, University of Greifswald, Greifswald bCenter for Biomedicine and Medical Technology Mannheim (CBTM), Research Division Cardiovascular Physiology, Medical Faculty, Mannheim, Heidelberg University, Mannheim, Germany.
authors: Philipp
authors: P
authors: Heumann
authors: Anna
authors: A
authors: Koenen
authors: Olga
authors: O
authors: Zavaritskaya
authors: Konrad
authors: K
authors: Schütze
authors: André
authors: A
authors: Ramm
authors: Torsten
authors: T
authors: Schlüter
authors: Antje
authors: A
authors: Steinbach
authors: Rainer
authors: R
authors: Rettig
authors: Rudolf
authors: R
authors: Schubert
authors: Olaf
authors: O
authors: Grisk
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D008638:Mesenteric Arteries / Q000502:physiology*; D051381:Rats; D012077:Renal Artery / Q000502:physiology*; D013562:Sympathectomy
chemical_list: D020746:Calcium Channels, L-Type