Background: Hypertension is increasingly becoming a matter of medical and public health importance. The maintenance of normal blood pressure requires a balance between cardiac output and total peripheral resistance (TPR). The endothelium, through the release of vasodilating factors, plays an important role in the control of TPR and hence blood pressure homeostasis. Transient Receptor Potential Vanilloid type 4 (TRPV4) is a mechanosensitive non-selective cation channel that is expressed on the endothelium and contributes to endothelium-mediated vasodilation. So far, no data are available about the morphological and functional status of this channel in hypertensive cases. Objectives: To compare the morphological and functional expression of TRPV4 in the mesenteric artery of normotensive and hypertensive rats. Methods: Young and adult Wistar-Kyoto rats (WKY-Y & WKY-A), as well as young and adult spontaneously hypertensive rats (SHR-Y & SHR-A) were involved in this study. Second order mesenteric arteries were isolated from male rats anesthetized with an intraperitoneal injection of ketamine (140mg/Kg) and xylazine (40mg/Kg) mixture. Isolated arterial segments, 2 mm in length, were mounted in a four-chamber wire myograph and pre-contracted with 4 µM phenylephrine. Then the effect of 5 µM 4αPDD (TRPV4 agonist) was investigated in the presence and absence of 1 µM HC067047 (TRPV4 antagonist), 100 µM L-NAME (nitric oxide synthase inhibitor), and endothelium. The morphological distribution of TRPV4 in the mesenteric arteries was investigated by immunostaining and the level TRPV4 mRNA expression was studied using Real-time PCR. Values are means ± S.E.M., compared by student t-test. Results: 4αPDD induced a relaxation response in the mesenteric arterial preparations (WKY-Y: 85.98%±4.18; n=5) that was markedly inhibited by HC067047 (18.3%±2.86; n=5; p<0.05), endothelium removal (19.93%±1.5; n=4; p<0.05) and L-NAME (28.18%±3.09; n=5; p<0.05). The 4αPDD-induced relaxation was significantly lower in SHR-Y compared to WKY-Y (SHR-Y: 70.96%±3.65; n=6, WKY-Y: 85.98%±4.18; n=5, p<0.05). Moreover, the 4αPDD-induced response was significantly lower in WKY-A than WKY-Y (WKY-A: 75.58%±1.3; n=5, WKY-Y: 85.98%±4.18; n=5, p<0.05). Immunostaining study showed immunofluorescent signal confined to the endothelial layer of mesenteric arteries. The expression of TRPV4 mRNA in SHR-Y was significantly lower than in WKY-Y (SHR-Y; 0.67RU±0.34; n=4, WKY-Y: 2.34RU±0.15; n=4, p<0.05). Furthermore, TRPV4 mRNA expression in WKY-A was lower than its expression in WKY-Y (WKY-A: 0.62RU±0.37; n=4, WKY-Y: 2.34RU±0.15; n=4, p<0.05). Conclusion: Stimulation of TRPV4, expressed on the endothelium of rat mesenteric artery, triggers an endothelium-mediated relaxation response that markedly decreases with hypertension and growing up due to downregulation of TRPV4 expression.