Localization and Effects of Calcitonin Gene‐Related Peptide in the Testicular Vasculature of the Rat

Abstract

ABSTRACT: Using laser Doppler flowmetry, the effects of unilateral intratesticular injection of calcitonin gene‐related peptide (CGRP) and CGRP8–37, a CGRP‐receptor antagonist, on right‐and left‐testicular blood flow and mean arterial pressure were studied on anesthetized adult rats. Calcitonin gene‐related peptide in doses of 5 and 50 ng increased blood flow 37 ± 11% (mean ± SEM, P < 0.05) and 30 ± 5% at 5 mm, but not 15 mm, away from the injection site, respectively. They did not influence mean arterial pressure nor blood flow in the contralateral testis. Five‐hundred nanogram doses increased testicular blood flow in the injected testis at a point 15 mm away from the injection site (22 ± 3%, P < 0.05) and caused a slight decrease in mean arterial pressure (‐12 ± 3%, P < 0.05). The highest dose, 5 μg, caused a large (‐39 ± 3%, P < 0.05) fall in mean arterial pressure within 1 minute after injection, and testicular blood flow was reduced in both the injected (‐9 ± 2%, P < 0.05, 15 mm away from injection site) and contralateral testis (‐20 ± 5%, P < 0.05). Pretreatment with 500 ng of the receptor antagonist, CGRP8‐37, did not significantly attenuate the blood flow increasing effect of 50 ng CGRP, nor did 50 μg CGRP8‐37 (given alone) influence basal testicular blood flow in the injected testis. Using immunohistochemistry, CGRP‐containing nerves were observed in the superior and inferior spermatic nerves, in the testicular artery, and in the veins leaving the testis but not in intratesticular blood vessels. Conclusions: 1) CGRP is a potent vasodilator in the testicular vasculature and it may be involved in the local regulation of testicular blood flow; 2) the testis has limited capacity to autoregulate and is consequently unable to maintain a constant testicular blood flow during large and rapid reductions in blood pressure, and 3) the local and systemic effects of vasodilators act in opposite directions in the testis.