Protein Kinase D1 (PKD1) Signaling Involvement in the Vascular Reactivity in Spontaneous Hypertensive Rats

Protein Kinase D1 (PKD1) Signaling Involvement in the Vascular Reactivity in Spontaneous Hypertensive Rats

• Autor
• Lorencini, PZ1*
• Co-autores
• Albuquerque, BMV1* , Silva, RFC1* , Nascimento, TB1** , Jacobsen, BB1** , Bossuyt, J2** , Stefanon, I1**
• Resumo

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  INTRODUCTION: Arterial hypertension (AH) is a multifactorial disease involving changes in vascular reactivity. Although blood vessels are known to express the protein kinase D1 enzyme (PKD1), their role in regulating vascular reactivity in AH is not clear. The objective of this study was to evaluate the participation of the PKD1 signaling pathway in vascular reactivity in spontaneous hypertensive rats (SHR). METHODS: Twenty male SHR, 3 months old, weighing 257 ± 4.5g, were used. The vascular reactivity of thoracic aortic rings, pre-contracted with 75 mM KCl, was evaluated in the concentration-response curves to phenylephrine and angiotensin II, in the presence of the selective PKD1 inhibitor, CID 3.2?M; L-NAME 100?M, non-selective inhibitor of the nitric oxide synthase (NOS); 1400W 1?M compound, selective iNOS inhibitor; N-?-hydrochloride-propyl-L-arginine 0.5?M, selective nNOS inhibitor (CEUA-Ufes 02/2020). The statistical analysis used was one-way ANOVA plus Tukey's post hoc. RESULTS: In the presence of intact vascular endothelium, CID reduced the vasoconstriction phenylephrine-induced, but did not modify the response to angiotensin II. However, the angiotensin II-dependent contraction increment, during endothelium removal (E-), was smaller in the presence of CID (Angiotensin 10-5 M: E=137,0±13% vs E-CID=89,9±3,3%* to KCl 75mM, *p<0,01). Perfusion with L-NAME prevented the reduction of the vasoconstriction induced by CID (Phenylephrine 10-3,5 M: Control=116,6±13,5%; CID=60,0±14,5%*; L-NAME=138,9±14,6%; L-NAME+CID=116,3±13,9% to KCl 75mM, *p<0,01). PKD1 inhibition reduced the increment in the contractile angiotensin II-dependent, during nNOS inhibition (N-?-hydrochloride-propyl-L-arginine=68.0±9.9% vs N-?-hydrochloride-propyl-L-arginine+CID=42.1±8.8% to KCl 75mM, *p<0,01). CONCLUSION: This result suggests that PKD1 signaling is involved in the vascular reactivity to ?-adrenergic and angiotensin II receptors, depending on the vascular NO bioavailability in the SHR animals.

   

• Palavras-chave
• Protein Kinase D1, SHR, Vascular Reactivity.
• Modalidade
• Comunicação oral
• Área Temática
• Sinalização celular