Hypertension and The Kidneys

HypertensionFor their size, the kidneys do an awful lot of work. Besides filtering the blood of potentially harmful substances, they secrete hormones that influence the manufacture of red blood cells and the absorption and metabolism of calcium. Another job is to monitor blood pressure and to take corrective action if it drops. The kidney does this by secreting a proteolytic enzyme called renin (not to be confused with rennin, the bovine enzyme that curdles milk and is used to make cheeses and junkets), whose function is to control another hormone, angiotensin, the polypeptide that constricts blood vessels. Angiotensin, especially angiotensin 2, is occasionally the target of blood pressure medications. This compound constricts the walls of arterioles and closes capillary beds, causing the kidney to reabsorb sodium while stimulating the adrenal cortex to release aldosterone, itself encouraging the kidney to reclaim still more sodium and, therefore, water. To add to this complicated cycle, angiotensin 2 prompts the pituitary to secrete vasopressin, yet another hormone that constricts blood vessels and elevates blood pressure, but also reduces excretion of urine by causing the kidney to reabsorb water. Because of this activity, vasopressin is also known as antidiuretic hormone, which conserves water stores in times of dehydration. All this spirited activity is directed by the brain.

We all realize that blood pressure (BP) involves the heart. In response to elevated BP, the heart releases two natriuretic peptides, type A and type B. (natri from ‘sodium’ and uretic from urine). These hormones relax the arterioles, inhibit the secretion of renin and aldosterone, and constrain the reabsorption of sodium ions by the kidney. This reduces reabsorption of water, so the volume of urine increases along with the volume of sodium in it. The net effect is to lower BP by reducing the volume of blood in the circulatory system. Whew! If ever you have heard the expression from Psalm 139:14 that mentions man being fearfully and wonderfully made, you now know what it means.

High blood pressure, usually anything above 140/90, can be caused by a number of things, including overweight, race, age, diet and exercise, family history, smoking, alcohol and stress levels. Healthy lifestyle can help. If there is such a thing as a worldwide hypertension epidemic, it may now be addressed by tackling a newfound cellular source in the brain, the targeting of which can reverse the condition. It has been found that angiotensin 2 is causative of hypertension because of the dysregulation of certain brain mechanisms involving the endoplasmic reticulum (Young, 2012).

The Endo What?
The endoplasmic reticulum is common to all eukaryotic cells—those that have a membrane-bound nucleus, genetic material organized within chromosomes, and organelles, such as mitochondria, chloroplasts…and endoplasmic reticula (ER). The ER is a network of membranes important to protein synthesis and folding, and it helps in the transport of cellular materials. The actual job of the ER varies from cell type to cell type, and occasionally within the same cell, depending on whether it is smooth or rough. The smooth ER is shaped like a tube and synthesizes phospholipids, which are the chief constituents of cell membranes. It also breaks down toxins in the liver, helps to regulate calcium concentrations, and controls the metabolism of carbohydrates. The rough ER is a line of flattened sacs with little bumps called ribosomes on the outside. This is where serum proteins, such as albumin, are synthesized.

Back To BP
Researchers have recently found that a water-soluble (hydrophilic) bile acid called tauroursodeoxycholic acid (TUDCA) reduces stress to the endoplasmic reticulum, which acts as a stress manager for every cell. If something goes wrong in a cell, the ER starts processes that help adapt to the stressors, angiotensin 2 among them. Because different ER’s do different jobs, only those that orchestrate the cascade of events causing hypertension are influenced by TUDCA. These are located outside the blood-brain barrier, near the bottom, allowing them to be affected by substances that are too large to cross the barrier, such as certain medications. Nonetheless, these ER’s are able to communicate with the brain’s inner chambers. TUDCA may then be able to treat the stress on hypertension-related endoplasmic reticula that control the release of angiotensin 2 (Young, 2012).

Chronic metabolic disorders, such as obesity, diabetes and insulin resistance are also mediated by the ER’s failure or success in launching an adequate stress defense.  Insulin resistance associated with the production of inflammatory factors, both related to fat cells, can activate the ER stress pathway. Research at the Hallet Diabetes Center of Brown University discovered that TUDCA reduces inflammatory signaling and thus may attenuate the ER stressors that trigger blood pressure elevation (Jiao, 2011). Additional study of intracellular regulatory proteins found that regular treatment with TUDCA lowers systolic blood pressure while lessening glucose intolerance (Ceylan-Isik, 2011).

Overactivity of the renin-angiotensin system, for which the kidneys are partly responsible, leads to the vasoconstriction that characterizes hypertension. It is easier to control angiotensin than renin, so angiotensin-related drugs are used, such as ACE inhibitors or angiotensin-receptor blockers (ARBs). It is renin that converts angiotensin. Renin blockers demonstrate poor bioavailability, so are rarely used. To avoid the side effects that accompany drugs, sodium reduction is the first step of a natural protocol in giving the kidneys a break and reducing BP. Following the DASH diet (Dietary Approaches to Stop Hypertension) is not a difficult strategy (Sacks, 2001) (Svetkey, 1999). Water will clear wastes from the kidneys, acidulation being recommended. Increase vegetable intake while reducing meat, especially red. Fill half the plate or more with produce. To bless the kidneys and to control BP add omega-3 fatty acids to the daily regimen (Friedman, 2010) (Cabo 2012) (Mori, 2010). If urine is any darker than a manila folder, drink more water.

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