Progression of hypertension and kidney disease in aging fawn-hooded rats is mediated by enhanced influence of renin-angiotensin system and suppression of nitric oxide system and epoxyeicosanoids
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
- Keywords
- Angiotensin II, chronic kidney disease, fawn-hooded rat, hypertension, proteinuria,
- MeSH
- Antihypertensive Agents pharmacology MeSH
- Kidney Glomerulus * metabolism physiopathology MeSH
- Hypertension * complications diagnosis metabolism physiopathology MeSH
- Angiotensin-Converting Enzyme Inhibitors pharmacology MeSH
- Blood Pressure drug effects MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Kidney Diseases etiology metabolism physiopathology prevention & control MeSH
- Nitric Oxide metabolism MeSH
- Disease Progression MeSH
- Proteinuria etiology metabolism physiopathology prevention & control MeSH
- Renin-Angiotensin System * drug effects physiology MeSH
- Aging metabolism MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antihypertensive Agents MeSH
- Angiotensin-Converting Enzyme Inhibitors MeSH
- Nitric Oxide MeSH
- Cytochrome P-450 Enzyme System MeSH
The fawn-hooded hypertensive (FHH) rat serves as a genetic model of spontaneous hypertension associated with glomerular hyperfiltration and proteinuria. However, the knowledge of the natural course of hypertension and kidney disease in FHH rats remains fragmentary and the underlying pathophysiological mechanisms are unclear. In this study, over the animals' lifetime, we followed the survival rate, blood pressure (telemetry), indices of kidney damage, the activity of renin-angiotensin (RAS) and nitric oxide (NO) systems, and CYP450-epoxygenase products (EETs). Compared to normotensive controls, no elevation of plasma and renal RAS was observed in prehypertensive and hypertensive FHH rats; however, RAS inhibition significantly reduced systolic blood pressure (137 ± 9 to 116 ± 8, and 159 ± 8 to 126 ± 4 mmHg, respectively) and proteinuria (62 ± 2 to 37 ± 3, and 132 ± 8 to 87 ± 5 mg/day, respectively). Moreover, pharmacological RAS inhibition reduced angiotensin (ANG) II and increased ANG 1-7 in the kidney and thereby may have delayed the progression of kidney disease. Furthermore, renal NO and EETs declined in the aging FHH rats but not in the control strain. The present results, especially the demonstration of exaggerated vascular responsiveness to ANG II, indicate that RAS may contribute to the development of hypertension and kidney disease in FHH rats. The activity of factors opposing the development of hypertension and protecting the kidney declined with age in this model. Therefore, therapeutic enhancement of this activity besides RAS inhibition could be attempted in the therapy of human hypertension associated with kidney disease.
b Department of Physiology Faculty of Science Charles University Prague Prague Czech Republic
c Department of Cardiology Institute for Clinical and Experimental Medicine Prague Czech Republic
e Department of Pathophysiology 2nd Faculty of Medicine Charles University Prague Czech Republic
References provided by Crossref.org
