Prenatal programming of hypertension induces sympathetic overactivity in response to physical stress

Abstract

Small-for-gestational-age infants are known to develop hypertension in adulthood. This prenatal programming of hypertension (PPH) can result from several insults including maternal dietary protein deprivation, uteroplacental insufficiency, and prenatal administration of glucocorticoids. The mechanisms underlying the development of hypertension remain unclear although the sympathetic nervous system has been indirectly implicated. This study was designed to directly measure renal sympathetic nerve activity both at rest and during physical stress in an animal model of PPH. The adult male offspring of rats fed either a 6% (PPH) or 20% protein diet (control) were investigated. Conscious systolic blood pressure measured by tail cuff was significantly higher in PPH compared with control (140 ± 3 versus 128 ± 3 mm Hg; P<0.05). Baseline mean arterial pressure, heart rate, and renal sympathetic activity were not different between groups during isoflurane anesthesia or after decerebration. Physical stress was induced in decerebrate animals by activating the exercise pressor reflex during static muscle contraction. Stimulation of the exercise pressor reflex evoked significantly larger changes from baseline in mean arterial pressure (40 ± 7 versus 20 ± 4 mm Hg; P<0.05), heart rate (19 ± 3 versus 5 ± 1 bpm; P<0.05), and renal sympathetic activity (198 ± 29% versus 68 ± 14%; P<0.05) in PPH as compared with control. The data demonstrate that the sympathetic response to physical stress is markedly exaggerated in PPH and may play a significant role in the development of hypertension in adults born small for gestational age.

Figure 1

Cardiovascular and sympathetic responses to EPR activation in representative control and PPH animals. The contraction-induced increases in ABP, HR and RSNA were larger in PPH compared to control.

Figure 2

Cardiovascular and sympathetic responses to activation of the EPR in control (n = 11) and PPH (n = 10) rats. A: peak response; B: integrated response. * P < 0.05 compared to control.

Figure 3

Cardiovascular and sympathetic responses to activation of the mechanically sensitive component of the EPR in control (n = 11) and PPH (n = 10) rats. A: peak response; B: integrated response.* P < 0.05 compared to control.

Figure 4

Cardiovascular and sympathetic responses to activation of the metabolically sensitive component of the EPR in control and PPH rats. A: Responses to the intra-arterial administration of 0.3 µg/100µL capsaicin in the hindlimb (control: n = 11; PPH: n = 10); B: Responses to the intra-arterial administration of 1.0 µg/100µL capsaicin in the hindlimb (control: n = 6; PPH: n = 6). * P < 0.05 compared to control.