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Chronic diabetes and hypertension impair the in vivo functional response to phenylephrine independent of α1-adrenoceptor expression.
Eur J Pharmacol. 2020 Jun 30; 883:173283.EJ

Abstract

Diabetes and hypertension can coexist and exacerbate each other. In the early stages of diabetes, there is a decreased vascular response of the sympathetic nervous system (SNS), probably due to lower expression of α1-adrenoceptors; however, it is unclear how diabetes in advanced stages changes the functionality of the SNS, especially the expression of α1-adrenoceptors. Thus, the aim of this work was to analyse the functional response to phenylephrine, a selective α1-adrenoceptor agonist, and the expression of α1-adrenoceptors in chronic diabetes and hypertension. Male SHR and WKY rats aged 10-12 weeks were administered either streptozotocin (60 mg/kg i.p.) or a vehicle (control group). Eight weeks after administration, dose-response curves to phenylephrine were generated and the gene and protein expression of α1-adrenoceptor subtypes (α1A-, α1B- and α1D-adrenoceptors) in the heart and aorta were measured. The response to phenylephrine was diminished in hypertensive rats and in normotensive diabetic rats. The coexistence of both diabetes and hypertension produced an even smaller response to phenylephrine than that observed for each condition separately. In the heart and aorta of diabetic rats, no changes in α1A-, α1B- or α1D-adrenoceptor mRNA expression were observed; however, protein expression was increased, mainly for the α1D-adrenoceptor. Hypertension increased mRNA and protein expression of α1-adrenoceptors in a tissue-dependent manner. The coexistence of both diabetes and hypertension produced differences in the regulation of mRNA and protein expression (increase or decrease) in both the heart and aorta. In conclusion, diabetes, hypertension and the coexistence of both pathologies impairs the in vivo response to phenylephrine. However, the differences in α1A-, α1B- and α1D-adrenoceptor expression cannot explain the reduced response to the agonist. This should be further explored in future experiments.

Authors+Show Affiliations

Laboratorio de Farmacognosia, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, Morelos, México; Bioquímica Clínica, Carrera de Químico Farmacéutico Biólogo, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, México.Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Baja California, Mexicali, Baja California, México.Departamento de Inmunología, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México.Departamento de Farmacología y Toxicología, Hospital Infantil de México "Federico Gómez", Ciudad de México, México.Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados, Ciudad de México, México.Laboratorio de Señalización Intracelular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México. Electronic address: svillafana@ipn.mx.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32619676

Citation

Rodríguez, Jessica E., et al. "Chronic Diabetes and Hypertension Impair the in Vivo Functional Response to Phenylephrine Independent of Α1-adrenoceptor Expression." European Journal of Pharmacology, vol. 883, 2020, p. 173283.
Rodríguez JE, Ruiz-Hernández A, Hernández-DíazCouder A, et al. Chronic diabetes and hypertension impair the in vivo functional response to phenylephrine independent of α1-adrenoceptor expression. Eur J Pharmacol. 2020;883:173283.
Rodríguez, J. E., Ruiz-Hernández, A., Hernández-DíazCouder, A., Huang, F., Hong, E., & Villafaña, S. (2020). Chronic diabetes and hypertension impair the in vivo functional response to phenylephrine independent of α1-adrenoceptor expression. European Journal of Pharmacology, 883, 173283. https://doi.org/10.1016/j.ejphar.2020.173283
Rodríguez JE, et al. Chronic Diabetes and Hypertension Impair the in Vivo Functional Response to Phenylephrine Independent of Α1-adrenoceptor Expression. Eur J Pharmacol. 2020 Jun 30;883:173283. PubMed PMID: 32619676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chronic diabetes and hypertension impair the in vivo functional response to phenylephrine independent of α1-adrenoceptor expression. AU - Rodríguez,Jessica E, AU - Ruiz-Hernández,Armando, AU - Hernández-DíazCouder,Adrián, AU - Huang,Fengyang, AU - Hong,Enrique, AU - Villafaña,Santiago, Y1 - 2020/06/30/ PY - 2020/03/26/received PY - 2020/06/09/revised PY - 2020/06/15/accepted PY - 2020/7/4/pubmed PY - 2020/7/4/medline PY - 2020/7/4/entrez KW - Diabetes KW - Hypertension KW - Phenylephrine KW - Spontaneously hypertensive rats KW - α(1)-adrenoceptors SP - 173283 EP - 173283 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 883 N2 - Diabetes and hypertension can coexist and exacerbate each other. In the early stages of diabetes, there is a decreased vascular response of the sympathetic nervous system (SNS), probably due to lower expression of α1-adrenoceptors; however, it is unclear how diabetes in advanced stages changes the functionality of the SNS, especially the expression of α1-adrenoceptors. Thus, the aim of this work was to analyse the functional response to phenylephrine, a selective α1-adrenoceptor agonist, and the expression of α1-adrenoceptors in chronic diabetes and hypertension. Male SHR and WKY rats aged 10-12 weeks were administered either streptozotocin (60 mg/kg i.p.) or a vehicle (control group). Eight weeks after administration, dose-response curves to phenylephrine were generated and the gene and protein expression of α1-adrenoceptor subtypes (α1A-, α1B- and α1D-adrenoceptors) in the heart and aorta were measured. The response to phenylephrine was diminished in hypertensive rats and in normotensive diabetic rats. The coexistence of both diabetes and hypertension produced an even smaller response to phenylephrine than that observed for each condition separately. In the heart and aorta of diabetic rats, no changes in α1A-, α1B- or α1D-adrenoceptor mRNA expression were observed; however, protein expression was increased, mainly for the α1D-adrenoceptor. Hypertension increased mRNA and protein expression of α1-adrenoceptors in a tissue-dependent manner. The coexistence of both diabetes and hypertension produced differences in the regulation of mRNA and protein expression (increase or decrease) in both the heart and aorta. In conclusion, diabetes, hypertension and the coexistence of both pathologies impairs the in vivo response to phenylephrine. However, the differences in α1A-, α1B- and α1D-adrenoceptor expression cannot explain the reduced response to the agonist. This should be further explored in future experiments. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/32619676/Chronic_diabetes_and_hypertension_impair_the_in_vivo_functional_response_to_phenylephrine_independent_of_α1-adrenoceptor_expression L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(20)30375-7 DB - PRIME DP - Unbound Medicine ER -
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