title: Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of alpha1- and alpha2-adrenoceptors on renal sensory nerve fibers.
abstract: Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating alpha-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the alpha(1)- and alpha(2)-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49 degrees C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 +/- 900 and 4,870 +/- 670%.s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 +/- 210%.s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 +/- 1 to 16 +/- 1 pg/min, and PGE(2) release, from 77 +/- 11 to 161 +/- 23 pg/min, suggesting a role for PGE(2) in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE(2). PGE(2) enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating alpha(1)- and alpha(2)-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE(2).
authors: Dept. of Internal Medicine, VA Medical Center, Bldg. 41, Rm 124, Highway 6W, Iowa City, IA 52246, USA. ulla-kopp@uiowa.edu
authors: Ulla C
authors: UC
authors: Kopp
authors: Michael Z
authors: MZ
authors: Cicha
authors: Lori A
authors: LA
authors: Smith
authors: Jan
authors: J
authors: Mulder
authors: Tomas
authors: T
authors: Hökfelt
mesh_terms: D000320:Adrenergic Fibers / Q000502:physiology*; D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000294:innervation*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D009476:Neurons, Efferent / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013373:Substance P / Q000378:metabolism; D013876:Thiophenes / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; C508711:L-161982; D050484:Norepinephrine Plasma Membrane Transport Proteins; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013876:Thiophenes; D014230:Triazoles; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D009638:Norepinephrine; D007213:Indomethacin