Angiotensin II blockade causes acute renal failure in eNOS-deficient mice.
Jürgen Schnermann1, Yuning G Huang2, Josie P Briggs2
1National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA, jurgens@ intra.niddk.nih.gov.
Journal of the Renin-Angiotensin-Aldosterone System : JRAAS
|January 18, 2017
Summary
Endothelial nitric oxide synthase (eNOS) deficiency increases blood pressure and renal vascular resistance. Angiotensin II is crucial for maintaining kidney function in eNOS knockout mice.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Molecular Biology
Background:
- Endothelial nitric oxide synthase (eNOS) plays a vital role in regulating vascular tone and blood pressure.
- Dysfunction of eNOS is implicated in various cardiovascular and renal diseases.
- Understanding the specific role of eNOS in renal hemodynamics is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the impact of eNOS deficiency on blood pressure, renal vascular resistance, and glomerular filtration rate.
- To determine the role of the renin-angiotensin system (RAS) in mediating these effects in eNOS knockout mice.
- To elucidate the compensatory mechanisms involved in maintaining renal function in the absence of eNOS.
Main Methods:
- Utilized adult eNOS knockout mice and wild-type littermates for comparative analysis.
- Measured blood pressure, renal vascular resistance, and glomerular filtration rate (GFR).
- Administered candesartan (AT1-receptor blocker) and assessed its effects on renal function.
- Evaluated renal renin expression through afferent arteriolar granularity.
Main Results:
- eNOS knockout mice exhibited significantly higher blood pressure and renal vascular resistance compared to wild-type mice.
- GFR was markedly reduced in eNOS knockout mice.
- AT1-receptor blockade with candesartan normalized blood pressure and renal vascular resistance but exacerbated the GFR reduction in eNOS knockout mice.
- Angiotensin-converting enzyme (ACE) inhibition similarly reduced GFR in eNOS knockout mice.
- Renal renin expression was reduced in eNOS knockout mice.
Conclusions:
- Chronic eNOS deficiency leads to hypertension and impaired renal hemodynamics.
- The renin-angiotensin system, particularly angiotensin II, plays a critical role in maintaining glomerular filtration pressure and GFR in eNOS-deficient mice.
- Targeting the RAS may have differential effects on renal function in the presence or absence of eNOS.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
1.3K
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
1.3K
01:29Acute Kidney Injury II: Pathophysiology
1.5K
Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
1.5K
01:25Antihypertensive Drugs: Direct Renin Inhibitors
1.7K
The renin-angiotensin-aldosterone system (RAAS) is an intricate physiological pathway involving numerous enzymes and hormones, including renin, angiotensin-converting enzyme (ACE), angiotensin I and II, and aldosterone. Imbalances within this system increase the production of angiotensin II and aldosterone. Increased angiotensin II levels promote vasoconstriction and blood pressure elevation. Concurrently, higher aldosterone levels stimulate sodium and water reabsorption in the kidneys,...
1.7K
01:30Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors
2.7K
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.7K
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers
2.9K
In the renin-angiotensin-aldosterone system, a hormone called angiotensin II plays a crucial role. It binds to the AT1 receptors in vascular smooth muscles coupled with Gq proteins. The activation of these receptors activates an enzyme called phospholipase C, which releases two molecules: inositol trisphosphate and diacylglycerol. These molecules cause a chain reaction that leads to the phosphorylation of myosin light chains and promotes interaction between actin and myosin, leading to smooth...
2.9K
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
434
Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
434