The accumulation of free zinc (Zn2+) appears to play a role in the neuronal degeneration that occurs after brain injury. Given that neonates respond to brain injury with increased plasticity compared to adults, this study compared the effect of age on free Zn2+ and the Zn2+-binding protein metallothionein-3 (MT-3) after injury. Unilateral cortical stab wounds were produced in 3-day-old and adult rats. Four weeks later, brains were removed for in situ visualization of free Zn2+ and measurement of MT-3 mRNA. Free Zn2+ and MT-3 mRNA accumulated after 4 weeks at the site of injury site when injury occurred in adults. However, 4 weeks after neonatal injury there was no increase in free Zn2+ or MT-3 mRNA in or around the site of injury.

We tested the hypothesis that intracerebroventricular (i.c.v.) administration of leptin would increase mean arterial pressure (MAP) in ad libitum (AL) fed and food deprived (FD) normotensive rats. Male Sprague–Dawley rats were chronically instrumented with a guide cannula directed at the lateral ventricle and a carotid arterial catheter. Following recovery from surgery, the MAP and heart rate (HR) response to i.c.v. administration of vehicle (5 μl saline over 1 min) or leptin (0.3 μg or 3.0 μg in 5 μl saline) were determined in conscious, unrestrained AL fed (n=7–10) and 48-h FD (n=5–10) rats. Food deprivation significantly reduced MAP (AL=116±3; FD=104±3 mmHg; P<0.01) without altering HR. In AL rats, high dose leptin (3.0 μg, i.c.v.) produced a significant increase in MAP when maximal responses were evaluated (9±2 mmHg; P<0.05), but did not significantly alter MAP and HR over time during the 90 min measurement period. In FD rats, low dose leptin (0.3 μg, i.c.v.) produced significant elevations in MAP (7±3 mmHg) after a latency of 60 min, while high dose leptin (3.0 μg, i.c.v.) produced an increase in MAP within the first 10 min (10±3 mmHg) followed by an additional increase 1 h after injection (6±2 mmHg). Leptin administration also produced delayed increases in HR in FD rats (0.3 μg, 34±5 b.p.m.; 3.0 μg, 57±10 b.p.m). These results indicate that leptin may modulate cardiovascular function through central mechanisms and may do so to a greater extent in food deprived animals.

Chronic food restriction reduces blood pressure (BP) and sympathetic support of BP in aortic coarctation hypertension. The purpose of this study was to test the hypothesis that chronic food restriction would reduce sympathetic support of BP mediated by the paraventricular hypothalamic nuclei (PVN). Hypertension was induced in male Sprague-Dawley rats (n=40) by suprarenal aortic coarctation. Rats were assigned to either an ad libitum fed (AL) group or a food restricted (FR) group that received 60% of the food consumed by AL for 3 weeks. One week prior to data collection, catheters were implanted in the left carotid artery and right jugular vein. BP was measured for 2 days prior to, and 7 days after rats in AL and FR groups received either bilateral electrolytic lesions of the PVN (PVNx) or sham lesions (SHAM). Prior to either PVNx or SHAM, FR rats had significantly lower BP (AL=152+/-5; FR=113+/-2 mmHg), less of a depressor response to ganglionic blockade (AL=-58+/-4; FR=-35+/-2 mmHg), and lower plasma norepinephrine levels (AL=758+/-71; FR=380+/-23 pg/ml) compared to AL. PVNx reduced BP in both AL and FR rats (AL-PVNx=105+/-6 mmHg, FR-PVNx=101+/-3 mmHg). PVNx also lowered the depressor response to ganglionic blockade (AL-PVNx=-28+/-5 mmHg, FR-PVNx=-29+/-4 mmHg) and plasma norepinephrine levels (AL-PVNx=372+/-74 pg/ml, FR-PVNx=248+/-31 pg/ml). FR decreased the magnitude of the reductions in resting BP and in sympathetic activity in response to PVNx. These results indicate that intact PVN are required for maintenance of aortic coarctation hypertension, and implicate the PVN as a site involved in BP reductions produced by chronic food restriction.

We examined the effects of short-term food deprivation on directly measured blood pressure and sympathetic support of blood pressure in male (n=7, 231+/-7 g) and female (n=91 193 +/- 4 g) spontaneously hypertensive rats (SHR, Charles River). Carotid arterial catheters were inserted under halothane anesthesia for direct assessment of cardiovascular function in conscious, unrestrained rats. After several days of recovery, mean arterial blood pressure (MAP) and heart rate (HR) were determined prior to, during, and after food deprivation Baseline MAP and HR were 170+/-14 mmHg and 351+/-13 beats/min in males and 187+/-6 mmHg and 354+/-9 beats/min in females. An overnight fast produced significant (P<0.05) reductions in MAP and HR After 48-hours of food deprivation, MAP was markedly reduced in males (-42+/-7 mmHg) and in females (-42+/-9 mmHg) Heart rate was significantly decreased during fasting in both males (-76+/-10 beats/min) and females (-60+/-11 beats/min) Caloric deprivation was accompanied by a significant reduction in sympathetic support of blood pressure (-32+/-8 mmHg in males; -21+/-7 mmHg in females) as determined by the depressor response to ganglionic blockade produced by hexamethonium/atropine (30.0/0.1 mg/kg) After three days of refeeding, MAP, HR and sympathetic support of blood pressure returned to values not significantly different from baseline. The results suggest that short-term food deprivation produces rapid reductions in MAP and HR in the SHR, which are mediated, at least in part, by reduced sympathetic tone (C) 1998 Elsevier Science Inc.

Objective To test the hypothesis that reductions in mean arterial pressure (MAP) induced by food-intake restriction in aortic coarctation hypertension are the result of a reduction of the sympathetic support of the MAP. We also wanted to determine whether the baroreflex control of the heart rate, and alpha-and beta-adrenergic responsivenesses were influenced by chronic food-intake restriction,Methods Four days after aortic coarctation, female Sprague-Dawley rats were assigned to a group that had access ad libitum to food (CON; n = 19) or to a food-intake-restricted group (FRG; n = 17) that was allowed 60%, of the CON group's food intake per rat. After 3 weeks, carotid and jugular catheters were implanted for measurement of the MAP and infusion of drugs into conscious rats. The sympathetic contribution to the blood pressure was assessed by measuring the depressor response to ganglionic blockade by hexamethonium plus atropine (30.0 and 0.1 mg/kg intravenously). The baroreflex control of the heart rate was assessed by administering alternating bolus doses of phenylephrine and nitroprusside, The alpha-adrenergic sensitivity was assessed by measuring the response of the MAP to phenylephrine in areflexive rats (after ganglionic blockade), and the beta-adrenergic sensitivity was assessed by measuring the responses of the MAP and heart rate to isoproterenol administration both in reflexive and in areflexive rats.Results Four days after catheterization, both the MAP (CON 150 +/- 5 mmHg, FRG 116 +/- 4 mmHg) and the heart rate (CON 414 +/- 8 beats/min, FRG 365 +/- 11 beats/min) were significantly lower in rats of the FRG. That the sympathetic support of the MAP had diminished in FRG rats was evidenced by an attenuated depressor response to ganglionic blockade (40 +/- 3 versus 65 +/- 3 mmHg). FRG rats exhibited significantly greater reflex bradycardia in response to phenylephrine (slope -1.44 +/- 0.07 versus -0.54 +/- 0.05 beats/min per mmHg), whereas their reflex tachycardia was not altered (slope -1.58 +/- 0.08 versus -1.53 +/- 0.13 beats/min per mmHg). FRG rats also displayed blunted responses of the heart rate and MAP to isoproterenol administration.Conclusion Food-intake restriction attenuates the rise in MAP which occurs after aortic coarctation significantly, The antihypertensive effect of food-intake restriction may be mediated via a reduction in sympathetic tone.

We tested the hypothesis that food restriction would attenuate the development of hypertension in spontaneously hypertensive rats (SHR). Furthermore, we hypothesized that food restriction would reduce the tonic sympathetic nervous system support of blood pressure in the SHR. Male SHR (Charles River, age 5 wk) were randomly assigned to ad libitum (ADLIB, n = 8) or food-restricted (FR, n = 9) groups. ADLIB rats were given free access to nonpurified diet and demineralized water. Food-restricted rats ate 60% of the amount of nonpurified diet consumed by rats in the ADLIB group. After 8 wk of treatment, ADLIB rats were heavier than FR rats (ADLIB = 318 ± 4 g; FR = 193 ± 5 g, P < 0.05). Blood pressure and heart rate (HR) were measured after chronic implantation of iliac arterial and jugular venous catheters. Food-restricted rats had lower mean arterial blood pressure (MAP) than ADLIB rats, measured in conscious, unrestrained state 4–6 h after catheterization (ADLIB = 162 ± 3 mmHg; FR = 142 ± 3 mmHg, P < 0.05) and measured on the day after surgery (ADLIB = 150 ± 6 mmHg; FR = 130 ± 3 mmHg, P < 0.05). There were no significant differences in resting HR on either day. Food-restricted rats exhibited augmented cardiac baroreflex-mediated bradycardia (bolus phenylephrine, 0.5–4.0 μg/kg intravenously) as assessed by linear slope of the ΔHR/ΔMAP relationship (ADLIB = −0.73 beats/(min⋅mmHg); FR = −1.62 beats/(min⋅mmHg), P < 0.05). Sympathetic support of blood pressure quantified by the depressor response to ganglionic blockade (hexamethonium 30 mg/kg; atropine 0.1 mg/kg intravenously), was greater in the ADLIB group (ADLIB: −59 ± 8 mmHg; FR: −36 ± 2 mmHg, P < 0.05). The results support the hypotheses that chronic food restriction reduces the development of hypertension and sympathetic support of MAP in spontaneously hypertensive rats.