Influence of hypertension development on rat tail artery responses to opioid peptides.
To determine whether the peripheral opioid system participates in hypertension development we studied responses to various opioid receptor agonists in field-stimulated isolated tail artery segments taken from spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats at different ages. The mu-selective agonist (DAGO) and the delta-selective D-Ala2-D-Leu5-enkephalin (DADLE) both suppressed the electrically stimulated vasoconstriction (EIC), but only in SHR arteries. The mu-selective antagonist beta-funaltrexamine reversed the effects of both DAGO and DADLE. Since the delta-selective antagonist ICI-174864 did not block DADLE inhibition, it is likely that both DAGO and DADLE effects were mu-receptor-mediated. Effects of DAGO and DADLE were qualitatively and quantitatively similar at all ages of SHR tested, and were not temporally related to hypertension development. Dynorphin (1-13) (DYN), a kappa-agonist, increased basal tone and EIC in all three rat strains. These responses were not blocked by nor-binaltorphimine, a selective kappa-opioid antagonist, suggesting that they may not involve kappa-receptor activation. There was a greater sensitivity to DYN at younger ages in all three rat strains and the sensitivity decreased with age. At 16 weeks when SHR hypertension was fully developed, SHR tail artery became almost totally insensitive to DYN in contrast to the continued responsiveness of 16-week-old WKY and SD arteries. The diminished effects to DYN in 16-week-old SHR tail arteries is suggestive of a compensatory mechanism to the hypertensive state. Collectively, the results establish that opioid receptor responses in SHR tail artery differ from those of normotensive rats. The significance of these differences to hypertension development in SHR remains to be determined.
Wong
S C
SC
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858-4354, USA.
Ingenito
A J
AJ
D000367:Age Factors; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology*; D004745:Enkephalins / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D010656:Phenylephrine / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists; D013623:Tail / Q000098:blood supply* / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D004745:Enkephalins; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D010656:Phenylephrine; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; C024524:beta-funaltrexamine; D004399:Dynorphins