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

Abstract

We hypothesized that hypothalamic NPYergic mechanisms mediate the blood pressure lowering effect of caloric restriction in hypertensive rats. Aortic coarctation-induced (AC) hypertensive rats ( n=25) were assigned to either an ad libitum fed control group (AL) or food restricted group (FR; 60% of AL consumption) for 3 weeks. Rats were instrumented chronically with vascular catheters and bilateral guide cannulae directed at the paraventricular hypothalamic nuclei (PVN). Blood pressure (BP) and heart rate (HR) responses to bilateral PVN microinjection of saline (200 nl) or the putative NPY receptor antagonists [ d-Trp 32]NPY (1–36) (3.3 μg/200 nl) and [ d-Tyr 27,36 Thr 32]NPY (27–36) ( d-NPY (27–36); 3.3 μg/200 nl) were determined. The FR rats were then refed and cardiovascular responses to PVN injections of NPY receptor antagonists were again determined. FR rats had significantly reduced 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 administration of [ d-Trp 32]NPY produced foraging behavior and concurrent increases in BP and HR in FR, AL and Re-fed rats. The behavioral activation suggests that [ d-Trp 32]NPY (1–36) produced activation of NPY receptors. In contrast, 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 increases in BP (peak=15±3 mmHg) which partially reversed the effect of FR on BP. Thus, in FR rats with reduced BP, PVN administration of an NPY receptor 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 NPYergic mechanisms may contribute to the reduction of BP produced by food restriction.