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NEUROHUMORAL CONTROL OF CIRCULATION AND HYPERTENSION

Stimulation of NPY Y₂ receptors by PYY_3-36 reveals divergent cardiovascular effects of endogenous NPY in rats on different dietary regimens

Applied Pharmacology, Biozentrum, Pharmazentrum, University of Basel, CH-4056 Basel, Switzerland

Submitted 9 July 2003 ; accepted in final form 2 October 2003

In the present experiments the gut hormone peptide YY_3-36 (PYY_3-36), 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, PYY_3-36 (300 µg/kg) or vehicle was injected intraperitoneally. In a third experiment, PYY_3-36 or vehicle was administered after 14 days of 50% restriction of a standard chow diet. In food-restricted rats, PYY_3-36 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, PYY_3-36 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 PYY_3-36 were observed in rats on different dietary regimens. These findings suggest that the cardiovascular effects of PYY_3-36 depend on the hypothalamic NPY release, which is increased after chronic food restriction and decreased during a high-fat diet.

blood pressure; heart rate; sympathetic nerve activity; neuropeptide Y; peptide YY

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