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Chronic treatment with C-type natriuretic peptide impacts differently in the aorta of normotensive and hypertensive rats

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Abstract

The aim of this study was to determine whether exogenous administration of C-type natriuretic peptide (CNP) induces functional and morphological vascular changes in spontaneously hypertensive rats (SHR) compared with normotensive rats. Male 12-week-old normotensive Wistar and SHR were administered with saline (NaCl 0.9%) or CNP (0.75 μg/h/100 g) for 14 days (subcutaneous micro-osmotic pumps). Systolic blood pressure (SBP) was measured in awake animals and renal parameters were evaluated. After decapitation, the aorta was removed, and vascular morphology, profibrotic markers, and vascular reactivity were measured. In addition, nitric oxide (NO) system and oxidative stress were evaluated. After 14-days of treatment, CNP effectively reduced SBP in SHR without changes in renal function. CNP attenuated vascular remodeling in hypertensive rats, diminishing both profibrotic and pro-inflammatory cytokines. Also, CNP activated the vascular NO system and exerted an antioxidant effect in aortic tissue of both groups, diminishing superoxide production and thiobarbituric acid-reactive substances, and increasing glutathione content. These results show that chronic treatment with CNP attenuates the vascular damage development in a model of essential hypertension, inducing changes in fibrotic, inflammatory, oxidative, and NO pathways that could contribute to beneficial long-term effects on vascular morphology, extracellular matrix composition, and function. The knowledge of these effects of CNP could lead to improved therapeutic strategies to not only control BP but also reduce vascular damage, primarily responsible for the risk of cardiovascular events.

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Acknowledgments

The authors thank Sandra Landín for secretarial work, Gabriela Noceti for technical assistance, and Ana Borthwick for proofreading and language assistance.

Funding

This study was funded by Universidad de Buenos Aires (UBA) [UBACYT: 200-201001-00060]; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) [PIP-112-201101-00581]; and Instituto de Química y Metabolismo del Fármaco (IQUIMEFA), UBA-CONICET, Argentina.

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Authors and Affiliations

  1. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Fisiología, Junín 956, piso 7, C1113AAD, Buenos Aires, Argentina

    Carolina Caniffi, Flavia M. Cerniello, Gonzalo Bouchet, María L. Sueiro, Analía Tomat & Cristina Arranz

  2. CONICET - Universidad de Buenos Aires, Instituto de la Química y Metabolismo del Fármaco (IQUIMEFA), Buenos Aires, Argentina

    Carolina Caniffi, Flavia M. Cerniello, Gonzalo Bouchet, María L. Sueiro, Analía Tomat & Cristina Arranz

  3. Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Inmunología, Buenos Aires, Argentina

    Daniel González Maglio

  4. CONICET - Universidad de Buenos Aires, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Buenos Aires, Argentina

    Daniel González Maglio

  5. Laboratorio de Medicina Experimental, Hospital Alemán, Buenos Aires, Argentina

    Jorge E. Toblli

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  1. Carolina Caniffi
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  2. Flavia M. Cerniello
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  6. Daniel González Maglio
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  7. Jorge E. Toblli
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  8. Cristina Arranz
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Contributions

•Conceived of or designed study: Carolina Caniffi, Cristina Arranz

•Performed research: Carolina Caniffi, Flavia M. Cerniello, Gonzalo Bouchet, María L. Sueiro, Analía Tomat, Daniel González Maglio, Jorge E. Toblli

•Analyzed data: Carolina Caniffi, Flavia M. Cerniello, Daniel González Maglio, Jorge E. Toblli

•Contributed new methods or models: Carolina Caniffi, Analía Tomat, Jorge E. Toblli, Cristina Arranz

•Wrote the paper: Carolina Caniffi, Analía Tomat, Cristina Arranz

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Correspondence to Carolina Caniffi.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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Dr. Jorge E. Toblli passed away in 2018

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Caniffi, C., Cerniello, F.M., Bouchet, G. et al. Chronic treatment with C-type natriuretic peptide impacts differently in the aorta of normotensive and hypertensive rats. Pflugers Arch - Eur J Physiol 471, 1103–1115 (2019). https://doi.org/10.1007/s00424-019-02287-y

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  • DOI: https://doi.org/10.1007/s00424-019-02287-y

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