Increased NPY activity in the PVN contributes to food-restriction induced reductions in blood pressure in aortic coarctation hypertensive rats

We hypothesized that hypothalamic NPYergic mechanisms mediate the blood pre ssure lowering effect of caloric restriction in hypertensive rats. Aortic c oarctation-induced (AC) hypertensive rats (n = 25) were assigned to either an ad libitum fed control group (AL) or food restricted group (FR; 60% of A L consumption) for 3 weeks. Rats were instrumented chronically with vascula r catheters and bilateral guide cannulae directed at the paraventricular hy pothalamic nuclei (PVN). Blood pressure (BP) and heart rate (HR) responses to bilateral PVN microinjection of saline (200 nl) or the putative NPY rece ptor antagonists [D-Trp(32)]NPY(1-36) (3.3 mu g/200 nl) and [o-Tyr(27,36) T hr(32)]NPY(27-36) (D-NPY(27-36); 3.3 mu g/200 nl) were determined. The FR r ats wers then refed and cardiovascular responses to PVN injections of NPY r eceptor antagonists were again determined. FR rats had significantly reduce d resting BP (159 +/- 4 vs. 129 +/- 4 mmHg) and HR (360 +/- 11 vs. 326 +/- 9 bpm) compared to AL controls. Refeeding restored BP and HR of FR rats to levels similar to AL (BP = 153 +/- 4 mmHg, HR = 359 +/- 11 bpm). PVN admini stration of [D-Trp(32)]NPY produced foraging behavior and concurrent increa ses in BP and HR in FR, AL and Re-fed rats. The behavioral activation sugge sts that [D-Trp(32)]NPY(1-36) produced activation of NPY receptors. In cont rast, D-NPY(27-36) did not produce any behavioral response or affect BP or HR in AL or Re-fed rats. In FR rats, D-NPY(27-36) produced significant incr eases in BP (peak = 15 +/- 3 mmHg) which partially reversed the effect of F R on BP. Thus, in FR rats with reduced BP, PVN administration of an NPY rec eptor antagonist increases BP. NPY blockade in the PVN accounted for about 50% of the BP effect of food restriction, thus other mechanisms are likely to be involved. These findings are consistent with the hypothesis that NPYe rgic mechanisms may contribute to the reduction of BP produced by food rest riction. (C) 1999 Elsevier Science B.V. All rights reserved.