Maternal Garlic Oil Supplementation Prevents High‐Fat Diet‐Induced Hypertension in Adult Rat Offspring: Implications of H2S‐Generating Pathway in the Gut and Kidneys

Abstract

Scope Perinatal high‐fat (HF) diet induces hypertension in adult offspring. Garlic, a naturally dietary source of Hydrogen sulfide (H2S) donor, has been shown benefits in hypertension. The article examines whether maternal garlic oil supplementation can prevent hypertension induced by HF diet and elucidate its protective effects. Methods and results Pregnant rats are given either a normal diet or HF diet. Rat dams are given garlic oil or vehicle daily by oral gavage at 100 mg kg‐1 day‐1 during pregnancy and lactation. Male offspring are sacrificed at 16 weeks of age. Garlic oil supplementation during pregnancy and lactation protected against hypertension induced by HF diet in adult male offspring. The beneficial effects of garlic oil are associated with increased renal mRNA expression and activity of H2S‐generating enzymes, increased NO bioavailability, increased plasma short chain fatty acid levels, and alterations of gut microbiota composition. Garlic oil supplementation increases abundance of genus Lactobacillus, but decreases genera Turicibacter and Staphylococcus. Conclusion The data reveals associations between H2S‐generating pathway in the gut and kidneys, NO system, gut microbiota, and microbiota‐derived metabolites in hypertension induced by HF intake and provide insight to garlic oil as a hypertension reprogramming strategy for further translational research.

Preventing Developmental Origins of Cardiovascular Disease: Hydrogen Sulfide as a Potential Target?

“…Although gut bacteria-derived H 2 S has been reported to display BP-lowering effect [125], there is still limited information on the role of microbes-derived H 2 S on cardiovascular programming. Recently, data obtained from our laboratory demonstrated that maternal NAC therapy that protected male SHR offspring against hypertension was linked to increased fecal concentrations of H 2 S and thiosulfate, augmentation of H 2 S-producing pathway in the kidneys, and alterations of gut microbiota [126]. As thiosulfate is a metabolite of H 2 S and also an index of the sulfide pool [127], our results suggest that targeting microbe-derived H 2 S might be a potential approach to prevent hypertension and deserves further evaluation.…”

“…As shown in Table 1, rats have been the dominant animal species used. Various developmental programming models have been studied, including the genetic hypertension model [93,136], suramin-induced preeclampsia model [57], N G -nitro-L-arginine-methylester (L-NAME) induced preeclampsia model [76], prenatal dexamethasone and postnatal high-fat diet [62], maternal hypertension [126], high-fat diet [128], maternal nicotine exposure [137,138], and maternal renovascular hypertension model [139,140]. The major adverse cardiovascular outcome is hypertension [57,62,76,93,126,128,139,140], followed by myocardial ischemia-reperfusion injury [137,138] and sympathetic activation [139,140].…”

“…Similarly, early NAC therapy, starting at four weeks of age, has proved beneficial for hypertension in SHRs [147]. As such, the use of NAC therapy in pregnancy and lactation has been shown to have benefits for hypertension of developmental origins in several animal models, including suramin-induced preeclampsia [57], prenatal dexamethasone and postnatal high-fat diet [62], L-NAME-induced preeclampsia [76], and maternal hypertension [126]. Although several H 2 S precursors in response to various insults that have been studied displayed protection against hypertension, there remains a lack of data regarding other cardiovascular benefits.…”

Animal Models for DOHaD Research: Focus on Hypertension of Developmental Origins

“…Data from many animal models indicate that gut microbiota dysbiosis may be involved in the developmental programming of hypertension. Various rat models of maternal insults such as hypertension [57], CKD [62], PCOS [65], TCDD exposure [82], minocycline use [92], a high-fructose diet [102], and a high-fat diet [126] have been examined with regard to the impact of gut microbiota dysbiosis on hypertension of developmental origins.…”

“…Third, the reprogramming effects of hydrogen sulfide (H 2 S)-based interventions have been shown in diverse animal models [145]. Currently available reprogramming interventions targeting the H 2 S pathway are L-cysteine [146], D-cysteine [146], NAC [147], sodium hydrosulfide [148], and garlic [126]. Finally, the targeting of nutrient-sensing signals such as cyclic adenosine monophosphate-activated protein kinase (AMPK) or peroxisome proliferator-activated receptor (PPAR) has been noted to regulate downstream target genes, thereby reprogramming hypertension induced by various maternal insults [149][150][151][152][153][154].…”