Prenatal hypoxia leads to increased muscle sympathetic nerve activity, sympathetic hyperinnervation, premature blunting of NPY signalling and hypertension in adult life.

William Rook, Christopher D. Johnson, Andrew M. Coney, Janice M. Marshall

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (≈3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1–5 and 6–10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ≈50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (≈9 months; 139±3 versus 126±3 mmHg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease
Original languageEnglish
Pages (from-to)1321-1327
Number of pages7
JournalHypertension
Volume64
Issue number6
Early online date29 Sep 2014
DOIs
Publication statusPublished - Dec 2014

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