Whether AICAR in Pregnancy or Lactation Prevents Hypertension Programmed by High Saturated Fat Diet: A Pilot Study.

Wan-Long Tsai,You-Lin Tain,Chien-Ning Hsu

doi:10.3390/nu12020448

Abstract

High consumption of saturated fats links to the development of hypertension. AMP-activated protein kinase (AMPK), a nutrient-sensing signal, is involved in the pathogenesis of hypertension. We examined whether early intervention with a direct AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) during pregnancy or lactation can protect adult male offspring against hypertension programmed by high saturated fat consumption via regulation of nutrient sensing signals, nitric oxide (NO) pathway, and oxidative stress. Pregnant Sprague–Dawley rats received regular chow or high saturated fat diet (HFD) throughout pregnancy and lactation. AICAR treatment was introduced by intraperitoneal injection at 50 mg/kg twice a day for 3 weeks throughout the pregnancy period (AICAR/P) or lactation period (AICAR/L). Male offspring (n = 7–8/group) were assigned to five groups: control, HFD, AICAR/P, HFD + AICAR/L, and HFD + AICAR/P. Male offspring were killed at 16 weeks of age. HFD caused hypertension and obesity in male adult offspring, which could be prevented by AICAR therapy used either during pregnancy or lactation. As a result, we demonstrated that HFD downregulated AMPK/SIRT1/PGC-1α pathway in offspring kidneys. In contrast, AICAR therapy in pregnancy and, to a greater extent, in lactation activated AMPK signaling pathway. The beneficial effects of AICAR therapy in pregnancy is related to restoration of NO pathway. While AICAR uses in pregnancy and lactation both diminished oxidative stress induced by HFD. Our results highlighted that pharmacological AMPK activation might be a promising strategy to prevent hypertension programmed by excessive consumption of high-fat food.

Highlights

Hypertension is a highly prevalent disease that can have a substantial impact on the global burden of cardiovascular disease in all world regions
(141 ± 24 positive cells) in the high saturated fat diet (HFD) + AIRCA/P group compared to that in the HFD group (Figure 5). These findings indicated that HFD downregulated AMPK/silent information regulator transcript 1 (SIRT1)/PGC-1α pathway, which can be restored by aminoimidazole-4-carboxamide riboside (AICAR) treatment in lactation and to a lesser extent in pregnancy
Because the interplay between ADMA-nitric oxide (NO) pathway and oxidative stress contributes to the pathogenesis of programmed hypertension [11,12], we further investigated whether AICAR treatment can mediate ADMA-NO pathway to prevent hypertension programmed by HFD (Table 3)

Summary

Introduction

Hypertension is a highly prevalent disease that can have a substantial impact on the global burden of cardiovascular disease in all world regions. The developmental origins of disease hypothesis (DOHaD). Suggests that the early life environment plays a key role in the early origins of hypertension [1,2]. Blood pressure (BP) is regulated by a complex process that contains key contributions from the kidney. Developmental programming of renal structure and function, namely renal programming [3], increases the risk for developing hypertension in adult life. Reprogramming intervention aimed at reversing the programming processes, preceding the onset of hypertension, to prevent or delay the development of hypertension [4].

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Discussion

Conclusion