Neuropeptide Y1- and Y2-receptor-mediated cardiovascular effects in the anesthetized guinea pig, rat, and rabbit.
Neuropeptide Y (NPY) causes vasoconstriction through Y1-receptors and inhibits vagal bradycardia through presynaptic Y2-receptors. These effects of NPY were investigated in anesthetized guinea pigs, rats, and rabbits to find the most suitable species for evaluation of Y1- and Y2-active agents in vivo. The increase in blood pressure (through Y1) of lower doses of NPY was similar in the three species (ED50, 0.9 +/- 0.13, 0.8 +/- 0.39, and 0.6 +/- 0.09 nmol/kg, respectively), but higher doses had depressor effects in four of six rats. Vagal bradycardia, induced by electrical stimulation of the right cervical vagus nerve, was inhibited by NPY in the guinea pig and in the rat (ED35, 3.5 +/- 0.46 and 11.2 +/- 1.79 nmol/kg, respectively; p < 0.05) but not in the rabbit. In the guinea pig, the Y2-receptor-preferring fragment NPY(3-36) and the selective Y1-receptor antagonist H 409/22 were used to confirm that the increase in blood pressure was mediated solely through the Y1-receptor and the vagal inhibition solely through the Y2-receptor. Aside from the cardiovascular effects, NPY caused a decrease in the body temperature and inhibited vagal bronchoconstriction in this species. Considering that NPY may cause depressor effects in the rat and has no effect on the vagal bradycardia in the rabbit, the guinea pig is preferable to both these species for assessment of Y1- and Y2-receptor-active agents in vivo.
Abrahamsson
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AstraZeneca Preclinical R & D Mölndal, Sweden. christina.abrahamsson@astrazeneca.com
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*
D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor