Mean arterial pressure regulation

Aldosterone acts on the distal tubule of the nephron to increase sodium reabsorption. The mechanism of action involves an increase in the number of sodium-permeable channels on the luminal surface of the distal tubule and an increase in the activity of the Na+-K+ ATPase pump on the basilar surface of the tubule. Sodium diffuses down its concentration gradient out of the lumen and into the tubular cells. The pump then actively removes the sodium from cells of the distal tubule and into the extracellular fluid so that it may diffuse into the surrounding capillaries and return to the circulation. Due to its osmotic effects, the retention of sodium is accompanied by the retention of water. In other words, wherever sodium goes, water follows. As a result, aldosterone is very important in regulation of blood volume and blood pressure. The retention of sodium and water expands the blood volume and, consequently, increases mean arterial pressure. 

Explain why mean arterial pressure must be closely regulated... 

Figure 15.5 Effects of sympathetic and parasympathetic nervous activity on mean arterial pressure. The parasympathetic nervous system innervates the heart and therefore influences heart rate and cardiac output. The sympathetic nervous system innervates the heart and veins and thus influences cardiac output. This system also innervates the arterioles and therefore influences total peripheral resistance. The resulting changes in cardiac output and total peripheral resistance regulate mean arterial pressure.

Renal blood flow has a direct effect on GFR, which in turn has a direct effect on urine output. As RBF increases, GFR and urine output increase. Conversely, as RBF decreases, GFR and urine output decrease. Furthermore, any change in urine output affects plasma volume and blood pressure. Therefore, the regulation of RBF and GFR are important considerations. According to Ohm s law (Q = AP/R), RBF is determined by mean arterial pressure (MAP) and the resistance of the afferent arteriole (Raffart) ... 

The generally accepted equation describing the hemodynamic factors regulating blood pressure may be expressed In the form BP = CO x TPR where BP Is the mean arterial pressure, CO the cardiac output, and TPR the total peripheral resistance. Using this simplified equation, it may be concluded that high blood pressure may result from a high cardiac output, a high total peripheral resistance, or a combination of the two. 

NO has a significant effect on vascular smooth muscle tone and blood pressure. Numerous endothelium-dependent vasodilators, such as acetylcholine and bradykinin, act by increasing intracellular calcium levels, which induces NO synthesis (Figure 19-2). Mice with a knockout mutation in the eNOS gene display increased vascular tone and elevated mean arterial pressure, indicating that eNOS is a fundamental regulator of blood pressure. The effects of vasopressor drugs are increased by inhibition of NOS. 

The primary mechanism of terbutaline is the stimulation of adenylcyclase, which catalyzes cyclic adenosine monophosphate (AMP) from adenosine triphosphate (ATP). In the liver, buildup of cyclic AMP stimulates glycogenolysis and an increase in serum glucose. In skeletal muscle, this process results in increased lactate production. Direct stimulus of sodium/potassium AT-Pase in skeletal muscle produces a shift of potassium from the extracellular space to the intracellular space. Relaxation of smooth muscle produces a dilation of the vasculamre supplying skeletal muscle, which results in a drop in diastolic and mean arterial pressure (MAP). Tachycardia occurs as a reflex to the drop in MAP or as a result of Pi stimulus. )Si-Adrenergic receptors in the locus ceruleus also regulate norepinephrine-induced inhibitory effects, resulting in agitation, restlessness, and tremor. 

Other factors regulating ADH secretion include blood volume and blood pressure. A decrease in blood volume of 10% or more causes an increase in ADH secretion sufficient to cause vasoconstriction as well as antidiuresis. A decrease in mean arterial blood pressure of 5% or more also causes an increase in ADH secretion. The resulting water conservation and vasoconstriction help increase... 

No explanation of hypertension will ever be complete without considering the role of the kidney. It has been postulated that the kidney may be the main controller of arterial pressure by means of its function to regulate fluid volume in the body. Higher sympathetic activity (NE levels) sustains blood pressure by inhibiting renal Na+ excretion. This hypothesis would explain the usefulness of natriuretic (Na+ excreting) diuretic effects. 

CYP4A inactivator Administration of a single dose of 10-SUYS, a potent and selective mechanism-based CYP4A inactivator, acutely reduced the mean arterial blood pressure as well as the urinary 20-HETE excretion in spontaneously hypertensive rats, consistent with the inactivation of renal 20-HETE formation ". These findings thus suggest that 20-HETE could play an important role in blood pressure regulation in hypertensive states and that the inhibition of its synthesis in these conditions may be of therapeutic benefit ". 

---