Hypertension (HTN) increases the risk for cardiac disease and stroke. Endogenous hydrogen sulfide (H 2 S), which plays a prominent role in a multitude of pathologies like inflammation/sepsis, hypertension, peripheral and cerebro-vascular, and coronary artery disease, is now well characterized as a physiologic vasodilator [1] . H 2 S is produced by cystathionine- γ -lyase (CSE) in vascular endothelium. It caters to relaxation through sulfhydration (posttranslational modification) of IK, SK and K ATP channels, resulting in vascular smooth muscle cell hyperpolarization. This effect is independent of the Nitric Oxide (NO)/cGMP/PKG axis [2] . Tang et al. studied H 2 S in spontaneously hypertensive (SHR) rats and demonstrated a loss of CSE/H 2 S in HTN and a decrease in BP (blood pressure) on substitution of H 2 S [3] . Aim To elicit if loss of endogenous H 2 S contributes to the pathogenesis of hypertension. Results Tail cuff was used to measure BP in SHR and control Wistar Kyoto (WKY) rats starting at age 4 weeks (w) up until SHRs became hypertensive. Infusion of glybenclamide (20 mg/kg) a K ATP channel blocker, revealed a significant increase in systolic BP (SBP) in 4-week-old SHR (ΔSBP = 43.16 ± 24.24%, n = 5) and 4 w WKY (ΔSBP = 89.97 ± 41.40%, n = 4), while little change was demonstrated in hypertensive 90 w SHR (ΔSBP = 24.07 ± 21.99%, n = 4), measured invasively via aortic catheterization.In a separate experiments, aortic rings isolated from age matched SHRs ( n = 5) and WKYs ( n = 5), were mounted on a myograph, prepared in physiologic buffer at 37 °C, and constricted with phenylephrine (1 μM), for assessment of endothelial function. Acetylcholine (ACH) dependent maximum relaxation on treatment with L-Name (eNOS inhibitor) was modestly attenuated in aortas of 4 w WKY (92.79 ± 2.64–83.26 ± 3.35%), 4 w SHR (83.50 ± 4.47–59.48 ± 8.75%) and 90-week-old WKYs (71.39 ± 15.06–15.77 ± 5.16%). Contrary to that, this response was completely blocked in 90 w SHRs (35.32 ± 5.16–0.24 ± 3.17%). Treatment with propargylglycine (CSE blocker) did not affect ACH mediated maximum relaxation in 90 w SHR (35.32 ± 5.16–29.40 ± 5.86%), but it significantly attenuated the responses in 4 w WKYs (92.79 ± 2.64–56.30 ± 4.55), 4 w SHRs (83.50 ± 4.47–71.63 ± 12.25) and 90 w SHRs (71.39 ± 15.06–8.13 ± 4.61%). Strikingly, rings from normotensive 16 w SHR had a complete L-Name sensitive attenuation of endothelial relaxation (63.25 ± 5.15–2.74 ± 1.75%). Conclusion There appears to be a NO independent component of endothelial relaxation in normotensive blood vessels, which is sensitive to CSE inhibitors and blockage of K ATP channels. This NO independent component of relaxation is absent in HTN and pre-HTN vessels; hence implying that loss of the CSE/H 2 S/K ATP axis could be a mechanism preceding HTN. We aims to measure CSE activity and sulfhydration of Kir 6.1-Cysteine 43 and GAPDH in normotensive/pre and post HTN blood vessels in different animal models of HTN to elicit if CSE/H 2 S/K ATP axis is a potential target for the treatment of hypertension.