FPR-1 (Formyl Peptide Receptor-1) Activation Promotes Spontaneous, Premature Hypertension in Dahl Salt-Sensitive Rats
| Autor: | Emily W. Waigi, Shaunak Roy, Nicole R. Bearss, Matam Vijay-Kumar, Sarah Galla, Piu Saha, Camilla F Wenceslau, Jonnelle M Edwards, Bina Joe, Jeremy C Tomcho, Blair Mell, Xi Cheng, Cameron G. McCarthy |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Dahl Salt-Sensitive Rats medicine.medical_specialty Blood Pressure 030204 cardiovascular system & hematology Mitochondrion Vascular Remodeling Bacterial Physiological Phenomena Formyl peptide receptor 1 Article Vascular remodelling in the embryo 03 medical and health sciences 0302 clinical medicine Internal medicine Internal Medicine medicine Animals Sodium Chloride Dietary Rats Inbred Dahl Cell Death Chemistry Receptors Formyl Peptide Gastrointestinal Microbiome Mitochondria Rats 030104 developmental biology Endocrinology Hypertension |
| Zdroj: | Hypertension |
| ISSN: | 1524-4563 |
| Popis: | Cell death has long been a characteristic phenotype of organ damage in hypertension, and recently, leaky gut has been revealed as a novel hypertensive phenotype. However, despite the increase in bacterial and damaged mitochondrial products in the circulation of hypertensive patients and animals, the mechanistic contribution of these two phenomena to hypertension pathophysiology is unknown. Mitochondria and bacteria both start protein translation with an N-formyl methionine residue and thus are the only sources of NFPs (N-formyl peptides), which activate the FPR-1 (formyl peptide receptor-1). We hypothesized that the synergistic action of bacterial and mitochondrial NFPs would cause the spontaneous elevation of blood pressure and vascular remodeling in male Dahl salt-sensitive rats via FPR-1. We observed that mitochondria-derived peptides originating from cell death in the kidneys are responsible for FPR-1–induced vascular hypercontractility and remodeling and premature elevation of BP in Dahl salt-sensitive rats fed a low-salt diet. However, a high-salt diet leads to gut barrier disruption and, subsequently, a synergistic action of mitochondria, and bacteria-derived leaky gut NFPs lead to a severe and established hypertension. Administration of an FPR-1 antagonist lowered blood pressure in Dahl salt-sensitive rats on a low-salt diet but amoxicillin administration did not. These results reveal for the first time that cell death can be a cause of hypertensive pathophysiology, whereas leaky gut is a consequence. |
| Databáze: | OpenAIRE |
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