Stimulation of NPY Y2 receptors by PYY3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens.
In the present experiments the gut hormone peptide YY3-36 (PYY3-36), which inhibits neuropeptide Y (NPY) release, was used as a tool to study the cardiovascular effects of endogenous NPY under different dietary regimens in rats instrumented with a telemetry transmitter. In a first experiment, rats were placed on a standard chow diet ad libitum and in a second experiment on a high-fat diet ad libitum. After 6 wk, PYY3-36 (300 microg/kg) or vehicle was injected intraperitoneally. In a third experiment, PYY3-36 or vehicle was administered after 14 days of 50% restriction of a standard chow diet. In food-restricted rats, PYY3-36 increased mean arterial pressure (7 +/- 1 mmHg, mean +/- SE, P < 0.001 vs. saline, 1-way repeated-measures ANOVA with Bonferroni t-test) and heart rate (22 +/- 4 beats/min, P < 0.001) during 3 h after administration. Conversely, PYY3-36 did not influence mean arterial pressure (0 +/- 1 mmHg) and heart rate (-8 +/- 5 beats/min) significantly in rats on a high-fat diet. Rats fed standard chow diet ad libitum showed an intermediate response (mean arterial pressure 4 +/- 1 mmHg, P < 0.05, and heart rate 5 +/- 2 beats/min, not significant). Thus, in our studies, divergent cardiovascular responses to PYY3-36 were observed in rats on different dietary regimens. These findings suggest that the cardiovascular effects of PYY3-36 depend on the hypothalamic NPY release, which is increased after chronic food restriction and decreased during a high-fat diet.
Nordheim
Ulrich
U
Applied Pharmacology, Biozentrum, Pharmazentrum, University of Basel, CH-4056 Basel, Switzerland.
Hofbauer
Karl G
KG
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology; D008297:Male; D009478:Neuropeptide Y / Q000502:physiology*; D010446:Peptide Fragments; D019894:Peptide YY / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*
D004041:Dietary Fats; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C061785:peptide YY (3-36)