Prenatal stress in the rat results in increased blood pressure responsiveness to stress and enhanced arterial reactivity to neuropeptide Y in adulthood

Abstract

We have shown previously that stress in the pregnant rat leads to a heightened cardiovascular response to restraint in adult offspring. The present study was undertaken to explore further the persistent cardiovascular effects of prenatal stress, with a focus on peripheral vascular function. Sprague-Dawley female rats were exposed to restraint/bright light three times daily in the last week of pregnancy. Litters from stressed and control females were cross-fostered to control dams to eliminate possible effects of maternal stress on nursing behaviour. At 120 days, offspring cardiovascular variables were measured by radiotelemetry. Reactivity of mesenteric small arteries was assessed by myography, and responses to electrical field stimulation determined. Resting cardiovascular parameters in prenatally stressed (PS) offspring were similar to controls but PS rats showed a greater increase in systolic blood pressure following restraint stress (P<0.05). Recovery was also prolonged in PS animals compared with controls and was of longer duration in PS females than in PS males (P<0.05). Adult PS females, but not males, also had elevated basal plasma corticosterone levels in comparison with controls (P<0.05). Vascular reactivity to neuropeptide Y (P<0.05) and electrical field stimulation (P<0.05) in mesenteric arteries was also significantly increased in PS animals. Vascular responses to adrenergic agonists as well as endothelial dilator function did not differ between PS and controls. We conclude that prenatal stress during late gestation has long-lasting effects on cardiovascular responsiveness and vascular reactivity to neuropeptide Y in the offspring.

Figure 1. Body weight change and food intake

Body weight change (A) and food intake (B) in control (▪, n= 10) and stressed mothers (^, n= 10) 10 days before and during pregnancy. *P < 0.05 control versus stressed dams.

Figure 2. Systolic and diastolic blood pressures

Systolic and diastolic blood pressures in female (A) and male (B) offspring of control (▪, n= 10) and stressed dams (•, n= 10) at 120 days of age. Values are expressed as the mean ±s.e.m. of 12 h night (n) and day (d) 12 h averages over 6 days (1–6).

Figure 3. Changes in systolic and diastolic blood pressure

Changes in systolic (A and B) and diastolic blood (C and D) pressure during 30 min of restraint and for 120 min following return to the home cage in the adult offspring of control (▪, n= 10) and stressed dams (•, n= 10). Data are expressed as the mean ±s.e.m. PS rats showed a greater increase in systolic arterial pressure (SAP) following restraint stress and extended SAP responses during recovery compared with controls (95 min versus 45 min). Diastolic arterial pressure (DAP) responses during stress and recovery did not differ between the groups. *P < 0.05 PS versus controls (repeated measures ANOVA).

Figure 4. Contractile responses

Contractile responses to neuropeptide Y (A), phenylephrine (B), noradrenaline (C) and electrical field stimulation (D) in small mesenteric arteries from control (▪, n= 10) and prenatally stressed (•, n= 10) rats. Responses to neuropeptide Y were determined on the arteries pre-activated with NA (80% of maximal constriction) and expressed as percentage of NA-induced tension. Significance was assessed by ANOVA: *P < 0.05 controls versus PS animals. The level of NA-induced pre-constrictor tension (mN mm⁻¹) were not different between experimental groups: control females 2.1 ± 0.2 (s.e.m.), PS females 2.06 ± 0.26, control males 2.14 ± 0.35, PS males 2.18 ± 0.13.

Figure 5. Relaxing responses

Relaxing responses to acetylcholine (A), dobutamine (B) and nitric oxide (C) in small mesenteric arteries from control (▪, n= 10) and prenatally stressed (•, n= 10) offspring rats.