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1 Chair for Applied Pharmacology, Biozentrum, Pharmazentrum, University of Basel, Basel, Switzerland
* To whom correspondence should be addressed. E-mail: karl.hofbauer{at}unibas.ch.
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 six weeks, PYY3-36 (300 µ/kg) or vehicle were injected intraperitoneally. In a third experiment PYY3-36 or vehicle were 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 ± SEM, p<0.001 vs. saline, One Way Repeated Measures ANOVA with Bonferroni t-test) and heart rate (+22 ± 4 beats/min, p<0.001) during 3 hours 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.
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