Japanese researchers have shown a new pathway by which the circadian clock influences hormone production and blood pressure in mice. Targeting the pathway in humans could be one way of combating hypetension.
Circadian Rhythms are our daily activity cycle that has been inherited from our forefathers and include body's natural cycles that control appetite, energy, mood, sleep and libido. These are delicately balanced cycles can get disturbed and then we suffer from a Circadian Rhythm Disorder.
Hypertension is the most common disease in humans, affecting over one billion people worldwide, and it is a major treatable risk factor in cardiovascular diseases such as stroke, myocardial infarction and kidney failure. Despite the importance of hypertension as a cause of cardiovascular disease, its pathogenesis is largely unknown.
Masao Doi and colleagues in the Kyoto University found increased activity of aldosterone biosynthetic enzyme in mice with a disrupted circadian clock may account for the increased aldosterone levels and salt-sensitive hypertension seen in these mice.
Aldosterone is a hormone that increases the reabsorption of sodium and water and the release (secretion) of potassium in the kidneys. This increases blood volume and, therefore, increases blood pressure. Conversely, drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives.
In their findings published in Nature Medicine, the Kyoto researchrs say, "Malfunction of the circadian clock has been linked to the pathogenesis of a variety of diseases. We show that mice lacking the core clock components Cryptochrome-1 (Cry1) and Cryptochrome-2 (Cry2) (Cry
-null mice) show salt-sensitive hypertension due to abnormally high synthesis of the mineralocorticoid aldosterone by the adrenal gland. An extensive search for the underlying cause led us to identify type VI 3â-hydroxyl-steroid dehydrogenase (Hsd3b6) as a new hypertension risk factor in mice. Hsd3b6
is expressed exclusively in aldosterone-producing cells and is under transcriptional control of the circadian clock."
Thus Hsd3b6 is in a pivotal position through which circadian clock malfunction is coupled to the development of hypertension. Translation of these findings to humans will require clinical examination of human HSD3B1
gene, which we found to be functionally similar to mouse Hsd3b6, the researchers add.