Abstract 029: Loss Of The Circadian Protein Per1 In The Dahl Salt-sensitive Rat Causes Exacerbation Of Diurnal Blood Pressure And Disruption Of Electrolyte Homeostasis

Autor: Adrian Zietara, Lashodya Dissanayake, Vladislav Levchenko, Michelle L Gumz, Alexander Staruschenko
Rok vydání: 2022
Předmět:
Zdroj: Hypertension. 79
ISSN: 1524-4563
0194-911X
Popis: Circadian rhythm is the 24-hr cycle experienced by most organisms which influences many physiological processes. Rhythms in physiological function are governed by a molecular circadian clock. Disruption of the circadian rhythm has been linked to deleterious cardiovascular outcomes, including the exacerbation of hypertension. The circadian clock is maintained by a group of transcription factors, including the protein Period 1 (encoded by PER1 gene), which regulate the expression of many different target genes in a tissue-specific manner. Previous studies in mice have shown that knockout of PER1 affects their ability to maintain proper sodium and blood pressure homeostasis. We hypothesized that the global knockout of PER1 on the Dahl salt-sensitive background (SS Per1-/- ) will affect the development of salt-sensitive blood pressure. Following the high salt diet, SS Per1-/- rats experienced reduced weight gain (344 ± 7 vs 280 ± 9 g, p+ /Cre, p=0.021), and exhibited reduced plasma potassium (3.6 ± 0.1 vs 3.0 ± 0.1 mM, p=0.005) and creatinine clearance (126.0 ± 23.8 vs 64.7 ± 5.9 mL/hr, p=0.008). Additionally, the SS Per1-/- group displayed increased renal tissue damage quantified by cortical fibrosis (0.9 ± 0.4 vs 6.2 ± 1.6 % area, p=0.011) and medullary protein casts (7.4 ± 0.9 vs 24.3 ± 4.0 % area, p=0.003). Examining the diurnal mean arterial pressure revealed no difference between SS and SS Per1-/- during their inactive day/light cycle (121.0 ± 1.8 vs 122.0 ± 1.9 mmHg, p=0.792), or their active night/dark cycle (127.2 ± 2.2 vs 127.6 ± 1.4 mmHg, p=0.883) when on a normal salt diet. However, after three weeks on a high salt 4% NaCl diet, SS Per1-/- animals experienced an exacerbated blood pressure during both the light (167.5 ± 3.7 vs 190.9 ± 7.2 mmHg, p=0.020) and dark (177.7 ± 3.4 vs 195.4 ± 4.5 mmHg, p=0.014) cycles. In the following analysis, we compared tissues, plasma, and electrolytes from SS Per1-/- and SS rats collected at 2 am and 2 pm. The conducted analysis revealed a number of pathways differently regulated during day and night cycles. In summary, our data indicate that global knockout of PER1 exacerbates salt-sensitive blood pressure development, disrupts electrolyte homeostasis, and aggravates renal damage.
Databáze: OpenAIRE
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