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 activity (RSNA) 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 to control (140 ± 3 vs. 128 ± 3 mmHg, P < 0.05). Baseline mean arterial pressure (MAP), heart rate (HR) and RSNA were not different between groups during isoflurane anesthesia or after decerebration. Physical stress was induced in decerebrate animals by activating the exercise pressor reflex (EPR) during static muscle contraction. Stimulation of the EPR evoked significantly larger changes from baseline in MAP (40 ± 7 vs. 20 ± 4 mmHg, P < 0.05), HR (19 ± 3 vs. 5 ± 1 bpm, P < 0.05) and RSNA (198 ± 29 vs. 68 ± 14 %, P < 0.05) in PPH as compared to 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.

Prenatal Hypoxia Leads to Increased Muscle Sympathetic Nerve Activity, Sympathetic Hyperinnervation, Premature Blunting of Neuropeptide Y Signaling, and Hypertension in Adult Life

“…In the only other study in which gross renal sympathetic nerve activity was recorded in male offspring of dams fed a low protein diet, baseline renal sympathetic nerve activity was comparable to that of controls, but showed larger increases during static muscle contraction. 26 In the few reports of single unit MSNA in humans, mean frequency of single unit MSNA was low in normotensives (≈0.3 Hz), higher in established essential hypertensives (≈0.6 Hz), and higher still in borderline hypertensives (≈0.75 Hz), consistent with sympathetic hyperactivity preceding the full development of essential hypertension. 27 Further, in normotensives, couplets or higher multiples of impulses were uncommon, instantaneous frequencies being <1 Hz in ≈50% of units, 28 but far more common in essential hypertension.…”

Dynamic exercise training prevents exercise pressor reflex overactivity in spontaneously hypertensive rats

“…This characteristic EPR overactivity has been shown to manifest not only in SHR but also in other models of the disease such as prenatally programmed hypertension (41,44) and angiotensin II-induced hypertension (24). In SHR, 3 mo of voluntary wheel running attenuated the cardiovascular and sympathetic responses to EPR activation.…”

Exercise pressor reflex in health and diseases: Animal studies

“…Recently, in the rat model of prenatal programming of hypertension (PPH), EPR dysfunction was found which may play a role in developing hypertension. Mizuno and colleagues 90) demonstrated that the RSNA and pressor responses to contraction were exaggerated in the PPH rats. Moreover, orally-administered treatment with angiotensin converting enzyme inhibitor enalapril in the PPH rats could reduce the exaggerated EPR responses 91) .…”