Renal sensory receptor activation by calcitonin gene-related peptide.
In anesthetized rats we examined whether calcitonin gene-related peptide activated renal pelvic sensory receptors and, if so, whether activation of renal pelvic calcitonin gene-related peptide receptors contributes to the inhibitory renorenal reflex response to renal mechanoreceptor stimulation. Calcitonin gene-related peptide (0.0026, 0.026, 0.26, and 2.6 mumol/L) administered into the renal pelvis increased ipsilateral afferent renal nerve activity in a concentration-dependent fashion (32 +/- 14%, 69 +/- 19%, 93 +/- 26%, and 253 +/- 48% [all P < .01], respectively). The increases in ipsilateral afferent renal nerve activity elicited by calcitonin gene-related peptide were associated with increases in contralateral urinary sodium excretion. The calcitonin gene-related peptide receptor antagonist human CGRP (h-CGRP) (8-37) (0.01, 0.1, 1.0, and 10 mumol/L) decreased the ipsilateral afferent renal nerve activity response to renal pelvic administration of calcitonin gene-related peptide (0.26 mumol/L) in a concentration-dependent fashion (29 +/- 4%, 33 +/- 12%, 76 +/- 9% [P < .01], and 86 +/- 13% [P < .01], respectively). In the presence of renal pelvic perfusion with vehicle, an increase in ureteral pressure of 5, 10, and 20 mm Hg increased ipsilateral afferent renal nerve activity by 13 +/- 7%, 41 +/- 7% (P < .01), and 95 +/- 15% (P < .01) and contralateral urinary sodium excretion by 8 +/- 1%, 24 +/- 4%, and 42 +/- 7% (all P < .05). The ipsilateral afferent renal nerve activity and contralateral natriuretic responses to graded increases in ureteral pressure (5 to 20 mm Hg) were unaltered by renal pelvic perfusion with h-CGRP (8-37) at 1.0 and 10 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)
Gontijo
J R
JR
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Kopp
U C
UC
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007668:Kidney / Q000294:innervation*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide