Related Experiment Video

Updated: Aug 8, 2026

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice
08:15

Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice

Published on: September 17, 2015

Enalapril and valsartan improve cyclosporine A-induced vascular dysfunction in spontaneously hypertensive rats

M Lassila1, P Finckenberg, A K Pere

  • 1Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Helsinki, P.O. Box 8, FIN-00014, Helsinki, Finland.

European Journal of Pharmacology
|June 17, 2000
PubMed

Insights

Cyclosporine A impairs renal artery function in hypertensive rats. Blocking the renin-angiotensin system with enalapril or valsartan protected against this vascular toxicity.

Area of Science:

  • Pharmacology
  • Nephrology
  • Cardiovascular Science

Background:

  • Cyclosporine A is known to induce hypertension and nephrotoxicity.
  • Its effects on arterial function, particularly in the context of high sodium intake during hypertension development, require further investigation.

Purpose of the Study:

  • To investigate the impact of long-term cyclosporine A treatment on in vitro arterial function in spontaneously hypertensive rats (SHR).
  • To evaluate the protective effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin AT(1) receptor antagonism against cyclosporine A-induced vascular dysfunction.

Main Methods:

  • Spontaneously hypertensive rats (SHR) were treated with cyclosporine A and a high-sodium diet for six weeks.
  • Concomitant treatment with enalapril (ACE inhibitor) or valsartan (AT(1) receptor antagonist) was administered to separate groups.
  • In vitro vascular preparations were used to assess arterial contractile and relaxation responses.

Main Results:

  • Cyclosporine A significantly impaired renal artery contractile responses to noradrenaline and angiotensin II.
  • Endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) relaxation responses in renal arteries were also severely reduced.
  • A trend towards mesenteric artery dysfunction was observed but did not reach statistical significance.
  • Both enalapril and valsartan significantly improved the impaired renal arterial functions.

Conclusions:

  • Cyclosporine A-induced hypertension and nephrotoxicity in SHR on a high-sodium diet are associated with significant renal arterial dysfunction.
  • Antagonism of the renin-angiotensin system, via ACE inhibition or AT(1) receptor blockade, offers protection against the vascular toxicity of cyclosporine A.

More Related Videos

A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis08:21

A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis

Published on: October 26, 2020

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion08:35

Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion

Published on: May 26, 2022

Related Concept Videos

Antihypertensive Drugs: Potassium-Sparing Diuretics01:28

Antihypertensive Drugs: Potassium-Sparing Diuretics

Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

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...
Antihypertensive Drugs: Angiotensin II Receptor Blockers01:30

Antihypertensive Drugs: Angiotensin II Receptor Blockers

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...
Antihypertensive Drugs: Direct Renin Inhibitors01:25

Antihypertensive Drugs: Direct Renin Inhibitors

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,...
Heart Failure Drugs: Diuretics01:22

Heart Failure Drugs: Diuretics

Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

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...