by Alicia M Prater PhD

Created on: August 04, 2009

Blood pressure is regulated by genetic and environmental factors that act together to maintain fluid and ion balance in the body. When this maintenance fails, disease may follow. Chronically high blood pressure, as occurs with high salt diets, is hypertension, which requires treatment to postpone cardiovascular and renal damage, which result in death. Under normal conditions, the body responds to its needs by keeping the blood pressure within normal limits while maintaining the fluid balance.

The Renin-Angiotensin System

One physiological system involved in the regulation of blood pressure is the renin-angiotensin system (RAS). The RAS s a multi-organ system of proteins and receptors regulated by hormones and cytokines to control a number of mechanisms associated with fluid balance and vasoconstriction. Angiotensin II (Ang II) is the active peptide in the RAS and exerts its effects by binding to its receptor, of which there are four known subtypes, though only two have been shown to be important in adult humans, and one is targeted for anti-hypertensive therapy. There is a circulating RAS in which the peptides act as endocrine hormones, and there are local systems in which Ang II is produced in that tissue and binds the receptor in that tissue for its specific functions. Ang II's precursor, angiotensinogen, is mainly produced in the liver, and the RAS is present in vascular smooth muscle cells, the heart, kidneys, adrenals, liver, fat tissue (adipocytes), and the brain.

Angiotensin II Effects

The Ang II receptors are membrane proteins, specifically G-proteins. When Ang II binds, the intracellular portion of the receptor changes its conformation and becomes a scaffold for signaling molecules within the cell. The type of signaling and its downstream effects depends on the receptor subtype that is bound.

In the kidney, Ang II affects blood pressure by modulating glomerular filtration and facilitating sodium retention; to retain fluid balance, water is retained with the sodium, increasing blood pressure. In vascular smooth muscle, Ang II induces vasoconstriction by binding the type 1 receptor, which reduces the vessel size, resulting in increased pressure. By binding the type 2 receptor, Ang II induces relaxation, which reduces blood pressure. Angiotensin II also induces the secretion of aldosterone from the adrenal glands via the type 1 receptor. Aldosterone is a hormone involved in sodium and fluid retention.

G-proteins and Tyrosine Kinase Signaling

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