Related Experiment Video

Updated: Jul 25, 2026

Assessing Murine Resistance Artery Function Using Pressure Myography
07:25

Assessing Murine Resistance Artery Function Using Pressure Myography

Published on: June 7, 2013

Alterations in the regulation of androgen-sensitive Cyp 4a monooxygenases cause hypertension

V R Holla1, F Adas, J D Imig

  • 1Department of Medicine, Vanderbilt University Medical School, Nashville, TN 37232, USA.

Proceedings of the National Academy of Sciences of the United States of America
|April 26, 2001
PubMed

Insights

Disrupting the Cyp 4a14 gene causes hypertension in mice, particularly in males. Androgens regulate this process, highlighting a new pathway for hypertension research.

Area of Science:

  • Biochemistry
  • Physiology
  • Genetics

Background:

  • Hypertension is a major global health issue, contributing significantly to cardiovascular, cerebral, and renal disease.
  • The specific genetic and molecular mechanisms underlying hypertension, especially sex-specific differences, require further elucidation.

Purpose of the Study:

  • To investigate the role of the Cyp 4a14 gene in the development of hypertension.
  • To explore the influence of androgens and P450 omega-hydroxylases in hypertension.

Main Methods:

  • Generation and analysis of Cyp 4a14 knockout (Cyp 4a14-/-) mice.
  • Measurement of blood pressure, plasma androgen levels, kidney Cyp 4a12 expression, and 20-hydroxyarachidonate formation.
  • Experimental manipulation including castration and androgen replacement.

Main Results:

  • Cyp 4a14 gene disruption leads to hypertension, more pronounced in male mice.
  • Hypertension in Cyp 4a14-/- mice is associated with elevated plasma androgens, increased kidney Cyp 4a12 expression, and higher 20-hydroxyarachidonate levels.
  • Castration reversed hypertension, while androgen replacement restored it, confirming androgen's role.

Conclusions:

  • Androgen-mediated regulation of Cyp 4a arachidonate monooxygenases is crucial for renal control of systemic blood pressure.
  • Cyp 4a14-/- mice serve as a valuable model for studying hypertension, sex hormones, and P450 omega-hydroxylases.
  • Human CYP 4A gene family members are potential candidates for investigating the genetic basis of human hypertension.

More Related Videos

Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats10:28

Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats

Published on: December 5, 2017

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

Related Concept Videos

Hormonal Regulation01:33

Hormonal Regulation

The renin-aldosterone system is an endocrine system which guides the renal absorption of water and electrolytes, thus managing blood pressure and osmoregulation. Activation of the system begins in the kidneys with a small cluster of cells adjacent to the afferent and efferent blood vessels of the renal corpuscle. As the nephrons are filtering blood, juxtaglomerular cells monitor blood pressure. If they detect a decrease in pressure, they release the hormone renin into the bloodstream.
Hypertension and Regulation of Blood Pressure01:18

Hypertension and Regulation of Blood Pressure

Hypertension, the most common cardiovascular disease, is diagnosed through repeated measurements of elevated blood pressure. Its risks, including damage to the kidney, heart, and brain, are directly proportional to blood pressure levels. Starting from 115/75 mm Hg, the risk of cardiovascular disease doubles with each increment of 20/10 mm Hg. The diagnosis relies on blood pressure measurements, not on patient symptoms, as hypertension is often asymptomatic until end-organ damage is imminent or...
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...
Hormonal Regulation of Blood Pressure01:17

Hormonal Regulation of Blood Pressure

Endocrinal or hormonal intervention in the cardiovascular system is predominantly exerted by the catecholamines - epinephrine and norepinephrine, as well as a slew of hormones that interact with renal function to modulate blood volume.
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction while...
Hypertension II: Pathophysiology01:29

Hypertension II: Pathophysiology

Hypertension is a chronic condition in which the blood's force against artery walls is excessively high, posing risks such as heart disease. The condition's underlying mechanisms involve complex interactions among the cardiovascular, kidney, and autonomic nervous systems.Renin-Angiotensin-Aldosterone System (RAAS): This system significantly influences blood pressure regulation. When blood pressure decreases, the kidneys secrete renin. This enzyme transforms angiotensinogen, a plasma protein,...