Harmane produces hypotension following microinjection into the RVLM: possible role of I(1)-imidazoline receptors

Abstract

The beta-carboline, harmane (0.1 - 1.0 nmol) produces dose dependent hypotension when microinjected unilaterally into the rostral ventrolateral medulla (RVLM) of the anaesthetized rat. The potency of harmane on blood pressure is similar to that of the imidazoline, clonidine. The hypotensive effects of both clonidine and harmane are reversed by microinjection of the relatively I(1)-receptor selective antagonist efaroxan (20 nmol). These results are consistent with harmane acting at an I(1)-receptor in the RVLM. This is the first report of an endogenous ligand for I(1)-receptors that has central effects on blood pressure.

Figure 1

Effect of drugs or vehicle when injected into the RVLM. 100 nL of each drug or vehicle was injected cumulatively at 15 min intervals. (A) Effect of vehicle, followed by efaroxan or clonidine, followed by efaroxan on MAP. (B) Effect of vehicle, followed by efaroxan or harmane, followed by efaroxan on MAP. (C) Effect of vehicle, followed by efaroxan or clonidine, followed by efaroxan on HR. (D) Effect of vehicle, followed by efaroxan or harmane, followed by efaroxan on HR. Basal values are given in Table 1. ^*Represents a significant difference from the matched control (P<0.05, two way ANOVA). +Represents a significant interaction between efaroxan and drug (P<0.05, two way ANOVA).