Hui Xie1, Patricio E Ray, Billie Lou Short. 1. Department of Neonatology, Children's Research Institute, Children's National Medical Center, The George Washington University, Washington, DC, USA.
Abstract
OBJECTIVE: Hypoxia/reoxygenation (H/R) associated with extracorporeal membrane oxygenation disrupts cerebral autoregulation. However, the underlying mechanisms remain poorly understood. The present study was designed to investigate the role of sensory C-fibers in myogenic responsiveness of cerebral arteries. METHODS: Arterial diameter and intraluminal pressure were simultaneously measured in vitro on rat posterior cerebral arteries. RESULTS: Cerebral arteries constricted in response to graded increase in intraluminal pressure (20-100 mmHg, in 20 mmHg increments). In vitro C-fiber desensitization with capsaicin (1 micromol/l, 20 minutes) significantly suppressed myogenic constriction by over 50%, but did not affect 5-hydroxytryptamine (0.01-10 micromol/l) and KCl (120 mmol/l)-induced constriction. Capsazepine (5 micromol/l, 30 minutes), a selective blocker of neuronal vanilloid receptor TRPV1, had similar inhibitory effect on cerebral myogenic constriction to elevated pressure. Cerebral myogenic constriction was significantly attenuated by H/R; the impairment by H/R was further enhanced after C-fiber desensitization (except at a pressure level of 100 mmHg). DISCUSSION: These findings indicate that C-fiber activity contributes to myogenic constriction of cerebral arteries under normal and H/R conditions. H/R-impaired myogenic responsiveness is exaggerated by C-fiber dysfunction. These results raise the possibility that therapeutic strategies directed toward preserving C-fiber nerve endings or supplying its constituent neuropeptides could be developed.
OBJECTIVE:Hypoxia/reoxygenation (H/R) associated with extracorporeal membrane oxygenation disrupts cerebral autoregulation. However, the underlying mechanisms remain poorly understood. The present study was designed to investigate the role of sensory C-fibers in myogenic responsiveness of cerebral arteries. METHODS: Arterial diameter and intraluminal pressure were simultaneously measured in vitro on rat posterior cerebral arteries. RESULTS: Cerebral arteries constricted in response to graded increase in intraluminal pressure (20-100 mmHg, in 20 mmHg increments). In vitro C-fiber desensitization with capsaicin (1 micromol/l, 20 minutes) significantly suppressed myogenic constriction by over 50%, but did not affect 5-hydroxytryptamine (0.01-10 micromol/l) and KCl (120 mmol/l)-induced constriction. Capsazepine (5 micromol/l, 30 minutes), a selective blocker of neuronal vanilloid receptor TRPV1, had similar inhibitory effect on cerebral myogenic constriction to elevated pressure. Cerebral myogenic constriction was significantly attenuated by H/R; the impairment by H/R was further enhanced after C-fiber desensitization (except at a pressure level of 100 mmHg). DISCUSSION: These findings indicate that C-fiber activity contributes to myogenic constriction of cerebral arteries under normal and H/R conditions. H/R-impaired myogenic responsiveness is exaggerated by C-fiber dysfunction. These results raise the possibility that therapeutic strategies directed toward preserving C-fiber nerve endings or supplying its constituent neuropeptides could be developed.
Authors: Ramona S Scotland; Sharmila Chauhan; Clare Davis; Carmen De Felipe; Stephen Hunt; Jahangir Kabir; Peter Kotsonis; Uhtaek Oh; Amrita Ahluwalia Journal: Circ Res Date: 2004-10-21 Impact factor: 17.367
Authors: Saurabh Gupta; Jair Lozano-Cuenca; Carlos M Villalón; René de Vries; Ingrid M Garrelds; Cees J J Avezaat; Jorge P van Kats; Pramod R Saxena; Antoinette MaassenVanDenBrink Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2007-02-13 Impact factor: 3.000