Perivascular adipose tissue (PVAT) and hydrogen sulfide (H2S) play important roles in the modulation of vasoactive responses and can interfere with the ethiopathogenesis of essential hypertension. The aim of this study was to evaluate the mutual relationship between PVAT and H2S (endogenously produced, exogenous) in vasoactive responses of isolated mesenteric arteries (MA) in adult normotensive (Wistar) and spontaneously hypertensive rats (SHR). In SHR, hypertension was associated with cardiac hypertrophy and increased contractility; however, there were no differences in the amount of retroperitoneal fat between strains. PVAT revealed the anti-contractile effect on vasoconstriction induced by exogenous noradrenaline in both strains, but surprisingly, this effect was stronger in SHR. Concurrently; PVAT exhibited a pro-contractile effect on contractions to endogenous noradrenaline released from arterial sympathetic nerves in SHR, but not in Wistar rats. We confirmed the anti-contractile effect of H2S in both, the vascular wall and PVAT of Wistar rats because the pre-treatment with propargylglycine (PPG), an inhibitor of H2S producing enzyme, significantly increased the noradrenaline-induced contraction. In SHR, H2S in the vascular wall exhibited a pro-contractile effect that was eliminated by the presence of PVAT; however, the pre-treatment with PPG did not affect noradrenaline contraction farther. Nevertheless, unlike in Wistar rats, the presence of PVAT potentiated the vasorelaxant effect of exogenously applied H2S in SHR. Our results confirmed that PVAT of MA and endogenously produced H2S could manifest as pro-contractile or as anti-contractile. In SHR, unlike in Wistar rats, the pro-contractile effect of PVAT associated with the stimulation of perivascular nerves, and the pro-contractile effect of H2S in the arterial wall could represent pathologic features. On the other hand, PVAT of SHR is endowed with compensatory vasoactive mechanisms, which include stronger anti-contractile action of an unknown factor (other than H2S) and potentiation of the vasorelaxant effect of exogenous H2S.