Cardiovascular complications are the main cause of death in patients with autosomal dominant polycystic kidney disease (ADPKD). Pkd1, the major gene involved in ADPKD, regulates Ca²⁺ signalling in epithelial cells and is expressed in the vascular wall. We used mice (males, 10 to 30 weeks) with a heterozygous deletion of Pkd1 (Pkd1+/-) and wild-type (WT, Pkd1+/+) littermates to test whether Pkd1 haploinsufficiency is associated with a vascular phenotype. Both groups had normal renal function and histology. Measure of systolic blood pressure by the tail cuff method showed similar values up to 20 weeks, but significantly higher pressure in 30 week-old Pkd1+/- compared to WT. However, telemetric recording of blood pressure in unrestrained animals did not reveal any difference between Pkd1+/- and WT. Renal hemodynamics in basal conditions was similar in both groups, but angiotensin II-evoked decrease in renal blood flow was significantly enhanced in Pkd1+/- mice. The contractile responses evoked by 100 mM KCl or by phenylephrine (0.01–10 mM) in aortas were increased in 30 week-old Pkd1+/- compared to WT, but there was no difference in younger animals. Aortas from 30 week-old Pkd1+/- were also less sensitive to the endothelium-dependent relaxing effect of acetylcholine. Basal cytosolic Ca²⁺ and KCl-evoked increase in cytosolic Ca²⁺ were significantly lower in Pkd1+/- aortas, whereas Ca²⁺ store release evoked by caffeine or thapsigargin was significantly larger. In contrast, phenylephrine evoked Ca²⁺ signal was unchanged. PCR analysis showed increased mRNA expression of Serca2a, Pkd2, and Trpc1 in the aorta, and of renin in the kidney from Pkd1+/- compared to WT. These results indicate that haploinsufficiency in Pkd1 is associated with an age-dependent increase in vascular reactivity, altered vascular intracellular Ca²⁺ homeostasis and compensatory changes in the expression of transport proteins involved in the Ca²⁺ signalling network.