Introduction:　Our　recent　findings　revealed　that　CACNA1D　D307G　mutation　participates　in　the　early-onset　hypertension.　Methods:　We　used　the　CRISPR/Cas9　technique　to　generate　the　Cacna1d　D307G　mutation　rat　model　and　investigated　the　effects　of　Cacna1d　D307G　mutation　on　blood　pressure　(BP)　and　renal　function.　Rats　fed　normal-salt　diet　had　normal　plasma　aldosterone　levels　but　higher　plasma　ET-1　and　mildly　elevated　systolic　BP　(SBP)　in　D307G　and　G307G　rats　compared　with　the　wild　type　(WT)　until　24　weeks.　Renal　function　and　renal　histopathology　did　not　significantly　differ　among　the　three　groups.　Results:　When　fed　high-salt　diet　(HSD),　D307G　and　G307G　rats　showed　more　sensitivity　to　HSD.　The　results　showed　a　further　increase　in　SBP　than　in　WT　rats.　Plasma　and　vascular　endothelin-1　(ET-1)　level　and　cortex　and　renal　artery　endothelin　type　A　(ETA)　receptor　protein　expression　were　significantly　increased.　Enhanced　renal　injury　was　also　noted　as　indicated　by　an　increased　ratio　of　kidney　weight/body　weight,　elevated　urinary　protein　and　albumin/creatinine　ratio,　higher　kidney　injury　molecule-1　(KIM-1)　levels,　advanced　fibrosis　and　apoptosis,　and　inflammation.　Further　experiments　revealed　a　reduction　in　urinary　sodium　excretion　and　creatinine　clearance.　Higher　protein　expression　of　renal　cortex　epithelial　sodium　channel　alpha　subunit　(alpha　ENaC)　was　confirmed　in　D307G　and　G307G　rats　fed　HSD.　However,　a　selective　ETA　receptor　blockade　(ABT-627)　could　partially　reverse　the　increased　SBP,　increased　serum　KIM-1　level,　upregulated　renal　cortex　protein　expression　of　alpha　ENaC,　and　reduced　urinary　sodium　excretion　with　reduced　creatinine　clearance　in　D307G　rats　fed　HSD.　Conclusion:　Activation　of　the　ET-1/ETA　system　in　D307G　mutation　rats　might　have　contributed　to　increased　sensitivity　to　salt　loading,　augmented　hypertension,　and　exacerbated　the　renal　injury.