Background/Objectives: The ACE2/Ang-(1–7)/Mas receptor axis is a protective, counterregulatory component of the RAAS that opposes Ang II/AT1R-mediated vasoconstriction. The present study evaluated the pharmacological effects of Ang-(1–7) in the rat inferior vena cava (IVC), a venous capacitance vessel involved in the regulation of venous return and cardiac preload. We hypothesized that Ang-(1–7) exerts anti-contractile effects in the rat inferior vena cava through activation of potassium channel-dependent mechanisms in venous smooth muscle. Methods: Isolated IVC rings from Wistar rats were studied using organ bath assays. Ang-(1–7) effects were assessed on pre-constriction induced by angiotensin II (Ang II), phenylephrine (PE), endothelin-1 (ET-1), and thromboxane A2 analog (U46619). Responses were recorded and quantified. Mechanistic involvement of nitric oxide (NO), prostaglandins, soluble guanylate cyclase (sGC), and K+ channels was evaluated using specific pharmacological inhibitors. Results: Ang-(1–7) attenuated Ang II-induced contraction. The effect was markedly reduced by tetraethylammonium (TEA), indicating a predominant role of potassium channel-dependent mechanisms in venous smooth muscle. In contrast, inhibition of nitric oxide synthase, soluble guanylate cyclase, or cyclooxygenase had minimal influence. Ang-(1–7) also produced concentrationdependent relaxation in PE-, ET-1-, and U46619-precontracted vessels, demonstrating agonist-dependent anti-contractile activity. Conclusions: Ang-(1–7) exerts significant anti-contractile effects in the rat inferior vena cava primarily through activation of TEAsensitive K+ channels in venous smooth muscle. These findings demonstrate functional activity of the ACE2/Ang-(1–7)/Mas axis in a major venous capacitance vessel and provide mechanistic insight into Ang-(1–7)-mediated modulation of venous tone, supporting further investigation in in vivo models.
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