Substance P mechanisms of the spinal cord related to vasomotor tone in the spontaneously hypertensive rat

Abstract

This report deals with substance P (SP) mechanisms involved in regulation of vasomotor tone at the spinal cord levels in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Our results indicate the following. (1) Intrathecal injections of the SP antagonist, d-Pro 4, d-Trp 7.9-SP 4–11 cause dose-dependent decreases in mean arterial pressure and heart rate in Sprague-Dawley rats, WKYs and SHRs; the maximal blood pressure decreases are equal to those seen after cervical spinal cord transection. (2) Intrathecal injections of this antagonist into the L1 spinal level in WKYs or SHRs that had previously had their C8 spinal cords transected caused a rise in blood pressure and heart rate, suggesting that intrinsic spinal SP mechanisms are probably not involved in vasomotor tone. (3) The intermediolateral cell column region (IML) of 16-week-old WKYs and SHRs has a single high affinity and saturable binding component with approximately the same dissociation constant ( K d = 1.21nM for WKYs; K d = 1.25nM for SHRs); the SHRs showed a higher number of sites (B max= 24.5fmol/mg protein) than WKY rats (B max= 19.9fmol/mg protein). The K d and B max obtained from IML sections from 4-week-old WKYs and SHRs exhibit no differences, although their binding values with 2 nM [ 3H]SP are higher than those obtained from the 16-week-old animals. (4) d-Pro 4, d-Trp 7,9-SP 4–11 has the same relatively low (micromolar range) potency for displacing [ 3H]SP binding in the IML of WKYs and SHRs ((5) SHRs (16 weeks old) contain 20% more SP immunoreactivity in the IML than WKY rats (834 ± 36pg/mg protein vs694 ± 50pg/mg protein); 4-week-old rats do not show such differences. The potential significance of these results is discussed in relation to the control of vasomotor tone.