Differential modulation by mu- and delta-opioids on baroreceptor reflex in conscious rabbits.
We examined the role of central mu- and delta-opioids on both neurohormonal responses and baroreceptor reflex in conscious rabbits. Both intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a mu-selective agonist, and [D-Ala2,D-Leu5]-enkephalin, a delta-selective agonist, caused dose-related increases in arterial pressure and renal sympathetic nerve activity, whereas intravenous injection of the same maximum dose of these peptides as that used in the intracerebroventricular experiment did not cause any cardiovascular and neuronal responses. On the other hand, increases in plasma epinephrine, norepinephrine, and glucose levels induced by intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin were significantly greater than those by [D-Ala2,D-Leu5]-enkephalin. Both enkephalins did not cause any responses in plasma renin activity, plasma vasopressin, and serum sodium and potassium concentrations. The sensitivity of the baroreceptor reflex control of renal sympathetic nerve activity using a logistic model was enhanced by a subpressor dose of intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10 pmol/kg) but not by [D-Ala2,D-Leu5]-enkephalin. Conversely, a mu-selective dose of intravenous naloxone (0.1 mg/kg) attenuated baroreceptor reflex sensitivity. Intravenous naloxone methobromide, which has been shown not to cross the blood-brain barrier, did not change baroreceptor reflex sensitivity, suggesting that naloxone acts at the central nervous system. In conclusion, in conscious rabbits, 1) intracerebroventricular mu- and delta-receptor agonists caused pressor responses and 2) mu-opioid agonist altered baroreceptor reflex control of renal sympathetic nerve activity and produced changes in sympathoadrenal responses.
Matsumura
K
K
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abe
I
I
Tominaga
M
M
Tsuchihashi
T
T
Kobayashi
K
K
Fujishima
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004723:Endorphins / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology*; D011817:Rabbits; D012018:Reflex / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D004723:Endorphins; D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D016308:Enkephalin, Leucine-2-Alanine