Obesity-Induced Hypertension

Hello everybody,

Today, I have chosen the following article to discuss.

Title: Obesity-Induced Hypertension

Subtitle: Interaction of Neurohormonal and Renal Mechanisms

Authors: John E. Hall, Jussara M. do Carmo, Alexandre A. da Silva, Zhen Wang, Michael E. Hall

Journal: Circulation Research. 2015;116:991-1006

Link: https://www.ahajournals.org/doi/abs/10.1161/circresaha.116.305697

My Commentary:

It has long been known that obesity is a big risk factor for the development of hypertension. However, the mechanisms through which it causes hypertension have been the subject of intense research. This article explains the neurohormonal and renal mechanisms through which hypertension develops and later is sustained in obese individuals.

There are three distinct mechanisms through which obesity causes hypertension to develop.

  1. Physical compression of the kidneys by fat in and around the kidneys
  2. Activation of the renin-angiotensin-aldosterone system
  3. Increased sympathetic nervous system activity

Physical compression of the kidneys by fat in and around the kidneys

It has been shown that increased visceral and retroperitoneal fat increases blood pressure by physically compressing the kidneys. The increased fat compresses the thin loops of Henle and vasa recta in the nephron, which leads to reduced renal tubular flow and medullary blood flow. Because of the reduced flow, more NaCl is reabsorbed in the loops of Henle which decreases the NaCl content of the fluid reaching the macula densa. This stimulates the macula densa which leads to two distinct outcomes through tubuloglomerular feedback. The first is to reduce afferent arteriolar resistance to increase glomerular blood flow to increase GFR. The second is to stimulate the juxtaglomerular cells (JG cells) to secrete renin, which causes increased blood pressure through the renin-angiotensin-aldosterone system (RAAS) which will be discussed later. Increased GFR and increased blood pressure then work to return macula densa NaCl delivery toward normal despite increased loop of Henle reabsorption, helping to restore sodium balance.

Activation of the Renin-Angiotensin-Aldosterone System (RAAS)

Obese subjects, especially those with visceral obesity, often have mild-to-moderate increases in plasma renin activity, angiotensinogen, angiotensin-converting enzyme (ACE) activity, angiotensin II and aldosterone. RAAS activation occurs despite NaCl retention, volume expansion, and hypertension, which typically suppress renin secretion and angiotensin II formation.

RAAS activation in obesity has been linked to compression of the kidneys by perinephric fat (discussed above) and increased sympathetic nervous system activity (discussed later). Renin is secreted by JG cells. Renin acts on angiotensinogen and converts it into angiotensin I. Angiotensin I is converted into angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II has major biologic activity. It constricts both afferent and efferent glomerular arterioles but efferent > afferent. The result is that glomerular filtration is preserved despite reduced glomerular blood flow due to constriction of afferent glomerular arterioles. The filtration fraction increases leading to less plasma fluid in the downstream peritubular capillaries which increases the osmotic gradient which causes more absorption of NaCl from the tubular fluid. Thus the tubular fluid reaching macula densa has low NaCl content which stimulates more renin secretion through tubuloglomerular feedback which leads to more angiotensin II formation and the whole cycle repeats itself.

The second major mechanism by which angiotensin II raises blood pressure is by formation of aldosterone in the zona glomerulosa of the adrenal cortex. Aldosterone acts on the principal cells of the distal tubule and the collecting ducts to increase sodium and water absorption which expands the blood volume to cause increased blood pressure.

Increased Sympathetic Nervous System (SNS) activity

Obese individuals have been shown to have increased renal sympathetic nervous system (RSNS) activity. This causes increased renin secretion which leads to more angiotensin II and aldosterone, which leads to hypertension by the mechanisms outlined above. The most important pathway which leads to increased SNS activity is leptin and CNS proopiomelanocortin (POMC) pathway. Leptin is a hormone produced by adipose tissue that acts on receptors in the hypothalamus, brainstem and sympathetic preganglionic neurons in the spinal cord. Leptin acts on proopiomelanocortin neurons (POMC) found in hypothalamus, brainstem and spinal cord intermediolateral nucleus (IML). This activation of POMC causes release of melanocyte-stimulating hormone (MSH) which acts on receptors in spinal cord IML nucleus to increase RSNS activity which leads to increased blood pressure by activation of RAAS as mentioned above.

It has to be said that more work needs to be done to further elucidate the mechanisms which cause obesity-induced hypertension. The sheer impact of obesity on hypertension can be estimated by the fact that 78% of primary hypertension in men and 65% in women can be ascribed to excess weight gain.

I thank you for taking the time to visit my website. We have a lot of work to do to defeat the menace of hypertension. Please join me in my quest to eradicate this disease from our planet. This is the best gift we can give to our future generations.

Kashif J. Piracha, MD
Houston, Texas
United States

 

 

 

 

 

 

 

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