Protective Role of Taurine on Rat Offspring Hypertension in the Setting of Maternal Chronic Kidney Disease

Abstract

Taurine is a natural antioxidant with antihypertensive properties. Maternal chronic kidney disease (CKD) has an impact on renal programming and increases the risk of offspring hypertension in later life. The underlying mechanisms cover oxidative stress, a dysregulated hydrogen sulfide (H₂S) system, dysbiotic gut microbiota, and inappropriate activation of the renin-angiotensin-aldosterone system (RAAS). We investigated whether perinatal taurine administration enables us to prevent high blood pressure (BP) in offspring complicated by maternal CKD. Before mating, CKD was induced through feeding chow containing 0.5% adenine for 3 weeks. Taurine was administered (3% in drinking water) during gestation and lactation. Four groups of male offspring were used (n = 8/group): controls, CKD, taurine-treated control rats, and taurine-treated rats with CKD. Taurine treatment significantly reduced BP in male offspring born to mothers with CKD. The beneficial effects of perinatal taurine treatment were attributed to an augmented H₂S pathway, rebalance of aberrant RAAS activation, and gut microbiota alterations. In summary, our results not only deepen our knowledge of the mechanisms underlying maternal CKD-induced offspring hypertension but also afford us the impetus to consider taurine-based intervention as a promising preventive approach for future clinical translation.

Keywords: chronic kidney disease; developmental origins of health and disease (DOHaDs); gut microbiota; hypertension; nitric oxide; renin–angiotensin–aldosterone system (RAAS); taurine.

Figure 1

Experimental design and animal grouping.

Figure 2

Systolic blood pressure in offspring from 3 to 12 weeks of age (n = 8/group). * p < 0.05 vs. C; # p < 0.05 vs. CKD. C = control offspring rats; CKD = adenine-exposed offspring rats; T = offspring rats born to dams which received taurine; CKDT = offspring rats born to adenine-treated dams which received taurine.

Figure 3

(A) Renal gene expression of H₂S-generating enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), 3-mercaptopyruvate sulphurtransferase (3MST), and d-amino acid oxidase (DAO). (B) Renal H₂S synthesis. * p < 0.05 vs. C; # p < 0.05 vs. CKD. C = control offspring rats; CKD = adenine-exposed offspring rats; T = offspring rats born to dams which received taurine; CKDT = offspring rats born to adenine-treated dams which received taurine.

Figure 4

Renal gene expression of renin-angiotensin-aldosterone system components, including renin, (pro)renin receptor (PRR), angiotensinogen (AGT), angiotensin converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R). * p < 0.05 vs. C; # p < 0.05 vs. CKD. C = control offspring rats; CKD = adenine-exposed offspring rats; T = offspring rats born to dams which received taurine; CKDT = offspring rats born to adenine-treated dams which received taurine.

Figure 5

Alpha and beta diversities among groups. Alpha diversity was significant for (A) Pielou’s evenness and (B) Shannon index. p < 0.05 vs. C. (C) Partial least squares discriminant analysis (PLS-DA) plots of beta diversity. Each dot represents the microbiota of a single sample, and dots of the same color belong to the same group. C = control offspring rats; CKD = adenine-exposed offspring rats; T = offspring rats born to dams which received taurine; CKDT = offspring rats born to adenine-treated dams which received taurine.

Figure 6

Linear discriminant analysis effect size (LEfSe) identified most differential taxa where LDA score thresholds > 4 were listed. C = control offspring rats; CKD = adenine-exposed offspring rats; T = offspring rats born to dams which received taurine; CKDT = offspring rats born to adenine-treated dams which received taurine.

Figure 7

Genus-based comparison between the CKD and CKDT groups. Relative abundance of (A) Bifidobacterium, (B) Asteroleplasma, (C) Dehalobacterium, and (D) Erisipelactoclostridium. The outliers are shown as dots. * p < 0.05; *** p < 0.005; **** p < 0.001. CKD = adenine-exposed offspring rats; CKDT = offspring rats born to adenine-treated dams which received taurine.

Figure 8

Schematic diagram summarizing the protective effects of perinatal taurine supplementation in male offspring born to dams with CKD and putative mechanisms. CKD = chronic kidney disease; H₂S = hydrogen sulfide; RAAS = renin–angiotensin–aldosterone system; BP = blood pressure.