Angiotensin II And ?1-Adrenergic Receptors Signal Transduction Involves Protein Kinase D1 (PKD1) Signaling

Angiotensin II And ?1-Adrenergic Receptors Signal Transduction Involves Protein Kinase D1 (PKD1) Signaling

• Autor
• Albuquerque, B.M.V.
• Co-autores
• Lorencini, P.Z. , Ferrari, R. , Botelho, T. , Jacobsen, B.B. , Bossuyt, J. , Stefanon, I.
• Resumo

• Angiotensin II and ?1-adrenergic receptors promote DAG and IP3 PKC-dependent vasoconstriction. Considering protein kinase D1 (PKD1) is DAG activated, in this study we evaluated the PKD1 pathway involvement in the vascular reactivity mediated by angiotensin II and ?1 adrenergic receptor. Aortic rings, pre-contracted with 75mM KCl, from male Wistar rats (309±5g, N=20) were used to evaluate concentration-response curves to phenylephrine and angiotensin II in the presence of CID 2011756 3.2?M, a selective PKD1 inhibitor; L-NAME 100?M, a non-selective inhibitor of the nitric oxide synthase (NOS); 1400W 1?M, a selective iNOS inhibitor; N-?-hydrochloride-propyl-L-arginine 0.5?M, a selective inhibitor of nNOS (CEUA-UFES 02/2020). The statistical analysis used was Student's t-test and one-way ANOVA plus post-hoc Tukey. The selective PKD1 inhibitor, CID, reduced the contractile response to angiotensin II, while it did not modify the contraction to phenylephrine (Rmax angiotensin II: Control=43.1±4.9 vs CID 29.6±4.7*% to 75mM KCl*, p<0,05). Endothelial (E-) removal amplified angiotensin II-mediated contraction during PKD1 inhibition (Rmax; CID= 29.6±4.7 vs E-CID 84.4±14.4*% to 75 mM KCl*, p<0.01). The contractile response to phenylephrine was increased during nNOS inhibition but it was not modified by CID. In the presence of CID, phenylephrine-mediated contraction, during eNOS inhibition, was amplified. Perfusion with L-NAME+CID did not modify the angiotensin II-induced contractile response. However, iNOS inhibition increased the contractile response to angiotensin II in the presence of CID (angiotensin II 10-5,5 M; CID= 29,6±4,7 vs iNOS+CID 57,4±10,7%, p<0,05). These results suggest that vasoconstriction mediated by ?-adrenergic receptors and angiotensin II involves PKD-dependent signaling and is counterbalanced by NO bioavailability.

• Palavras-chave
• Protein kinase D1, Vascular reactivity, Angiotensin II, ?1 adrenergic receptor
• Modalidade
• Pôster
• Área Temática
• Sinalização celular