Kappa opioid receptors modulate cardiorespiratory function in hindbrain nuclei of rat

Abstract

The respiratory and cardiovascular effects of selective kappa opioid agonists were compared following microinjection (0.1 microliter) into the nucleus ambiguus (NA) and the nucleus tractus solitarius (NTS) regions of spontaneously breathing and artificially respired pentobarbital-anesthetized rats. In spontaneously breathing animals, the benzomorphan derivative MRZ 2549 (MRZ, 3 X 10(-11) to 16 X 10(-9) mol) elicited dose-related decreases of mean arterial pressure (MAP), heart rate (HR), and tidal volume (TV) following NA injection; bremazocine (BREM) decreased MAP, HR, and respiratory rate (RR). Following NTS injection, MRZ (3 X 10(-10) to 16 X 10(-9) mol) lowered MAP and TV, the highest dose also lowering HR and RR; BREM (3 X 10(-9) to 16 X 10(-9) mol) decreased MAP and HR. Naloxone (200 micrograms/kg, i.v.) reversed the respiratory effects of MRZ without consistently altering cardiovascular activity. In ventilated animals, NA injections of MRZ or BREM (3 X 10(-9) to 16 X 10(-9) mol) elicited a dose-related decrease of MAP without altering HR. These responses were not reversed by naloxone. The stereoisomer of BREM (+ BREM) was without effect at similar doses (3 X 10(-9) to 16 X 10(-9) mol). MRZ (16 X 10(-9) mol) elicited a naloxone-reversible tachycardia following NTS injection in ventilated animals; no other cardiovascular responses were observed following NTS administration of BREM (16 X 10(-9) mol) or lower doses of MRZ. Dynorphin (1-13) (6 X 10(-9) to 60 X 10(-9) mol) significantly lowered MAP without altering HR following NA microinjections in ventilated animals; the lower dose decreased MAP following NTS injections.(ABSTRACT TRUNCATED AT 250 WORDS)