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 nerve s in desoxycorticosterone acetate-salt (DOCA) hypertension, a low-reni n model of hypertension, is controversial. The present study was desig ned to determine if spinal substance P (SP) and/or calcitonin gene-rel ated peptide (CGRP) in ARN affects the development of 1K-WRAP or DOCA hypertension in adult rats. Selective long-term partial depletion of s pinal SP and CGRP within small primary afferent nerve fibers including unmyelinated ARN was achieved by intrathecal administration of capsai cin. After capsaicin treatment, 1K-WRAP hypertension was induced by re moving the right kidney and wrapping the left kidney with a figure-8 l igature. In a second group of rats, DOCA hypertension was induced by s ubcutaneous application of desoxycorticos-terone pellets after unilate ral nephrectomy. Systolic arterial pressure was monitored for 8 weeks by tail cuff plethysmography after which direct blood pressure measure ment was performed followed by immunohistochemistry. Intrathecal capsa icin administration had no significant effect on SP-ir and CGRP-ir of ARN soma located within thoracic dorsal root ganglia whereas immunorea ctivity against these peptides was reduced by one third to one half in the dorsal horn, indicating effective long-term spinal depletion of t hese neuropeptides. Intrathecal capsaicin enhanced the development of 1K-WRAP hypertension, since arterial pressure was greater in the treat ed group. In contrast, DOCA hypertension was unaffected by capsaicin p retreatment. 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 cap saicin-sensitive unmyelinated primary afferent neurons in the lower th oracic spinal cord may ameliorate 1K-WRAP hypertension, but not DOCA h ypertension.