Intrathecal capsaicin enhances one-kidney renal wrap hypertension in the rat.
Afferent renal nerves (ARN) have been implicated in the development of one-kidney renal wrap (1K-WRAP) hypertension. The role of renal nerves in desoxycorticosterone acetate-salt (DOCA) hypertension, a low-renin model of hypertension, is controversial. The present study was designed to determine if spinal substance P (SP) and/or calcitonin gene-related peptide (CGRP) in ARN affects the development of 1K-WRAP or DOCA hypertension in adult rats. Selective long-term partial depletion of spinal SP and CGRP within small primary afferent nerve fibers including unmyelinated ARN was achieved by intrathecal administration of capsaicin. After capsaicin treatment, 1K-WRAP hypertension was induced by removing the right kidney and wrapping the left kidney with a figure-8 ligature. In a second group of rats, DOCA hypertension was induced by subcutaneous application of desoxycorticosterone pellets after unilateral nephrectomy. Systolic arterial pressure was monitored for 8 weeks by tail cuff plethysmography after which direct blood pressure measurement was performed followed by immunohistochemistry. Intrathecal capsaicin administration had no significant effect on SP-ir and CGRP-ir of ARN soma located within thoracic dorsal root ganglia whereas immunoreactivity against these peptides was reduced by one third to one half in the dorsal horn, indicating effective long-term spinal depletion of these neuropeptides. Intrathecal capsaicin enhanced the development of 1K-WRAP hypertension, since arterial pressure was greater in the treated group. In contrast, DOCA hypertension was unaffected by capsaicin pretreatment. Considering the neurotoxic action of capsaicin for SP-ir and CGRP-ir unmyelinated primary afferent neurons, we hypothesize that spinal SP, CGRP and/or related peptides existing in ARN and other capsaicin-sensitive unmyelinated primary afferent neurons in the lower thoracic spinal cord may ameliorate 1K-WRAP hypertension, but not DOCA hypertension.
Burg
M
M
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, MO 63104.
Zahm
D S
DS
Knuepfer
M M
MM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000502:physiology
D013373:Substance P; D003900:Desoxycorticosterone; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin