In spontaneously hypertensive rats, the KD increases hypertension,279,280 impairs endothelium-dependent relaxation in mesenteric arteries,280 causes renal damage279 and aggravates interstitial fibrosis and inflammatory responses in the heart.281 In the rat, The KD exacerbated disorders of glucose and lipid metabolisms and activated the renin-angiotensin-aldosterone system,279 and the ketone body might reduce eNOS expression via NF-κB singling pathway in vein endothelial cells,280 which could collectively contribute to hypertension and endothelial dysfunction. The gene discussed is REN; the disease is hypertensive disorder.