• Cardiac output is a function of stroke volume and heart rate. The most important determinant of stroke volume is the filling pressure, which is regulated through sodium homeostasis and its effect on blood volume. Heart rate and myocardial contractility (a second factor affecting stroke volume) are both regulated by the αand β-adrenergic systems (in addition to their effects on vascular tone).
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LOCAL FACTORS Autoregulation pH, hypoxia
Fig. 10.3 Bloodpressureregulation.
• Peripheral resistance is regulated predominantly at the level of the arterioles by neural and humoral inputs. Vascular tone reflects a balance between the actions of vasoconstrictors (including angiotensin II, catecholamines, and endothelin) and vasodilators (including kinins, prostaglandins, and NO). Resistance vessels also exhibit autoregulation, whereby increased blood flow induces vasoconstriction to protect tissues against hyperperfusion. Finally, blood pressure is fine-tuned by tissue pH and hypoxia to accommodate local metabolic demands.
Factors released from the kidneys, adrenal glands, and myocardium interact to influence vascular tone and to regulate blood volume by adjusting sodium balance (
Fig.
10.4 ). Each day, the kidneys on average filter 170 liters of plasma containing 23 moles of salt. Thus, with a typical diet containing 100 mEq of sodium, 99.5% of the filtered salt must be reabsorbed to maintain total body sodium levels. About 98% of the filtered sodium is reabsorbed by several constitutively active transporters. Recovery of the remaining 2% of sodium occurs by way of the epithelial sodium channel (ENaC), which is tightly regulated by aldosterone, a downstream effector of the renin-angiotensin system; it is this pathway that determines net sodium balance.
Kidneys influence peripheral resistance and sodium excretion/retention primarily through the reninangiotensin system. The kidneys and heart contain cells that sense changes in blood pressure and/or blood volume. In response, these cells release several important regulators that act in concert to maintain normal blood pressure:
Renin is a proteolytic enzyme produced by renal juxtaglomerular cells—myoepithelial cells that surround the glomerular afferent arterioles. It is released in response to low blood pressure in afferent arterioles, elevated levels of circulating catecholamines, or low sodium levels in the distal convoluted renal tubules. The latter occurs when the glomerular filtration rate falls (e.g., when the cardiac output is low) because a higher fraction of the filtered sodium is resorbed in the proximal tubules.
Angiotensin. Renin cleaves plasma angiotensinogen to angiotensin I, which in turn is converted to angiotensin
II by angiotensin-converting enzyme (ACE) in the periphery. Angiotensin II raises blood pressure by (1) inducing vascular SMC contraction, (2) stimulating aldosterone secretion by the adrenal gland, and (3) increasing tubular sodium resorption.
Vasodilators. The kidney also produces a variety of vascular relaxing substances (including prostaglandins and NO) that presumably counterbalance the vasopressor effects of angiotensin.
Aldosterone. Adrenal aldosterone increases blood pressure by its effect on blood volume; aldosterone increases sodium resorption (and thus water) in the distal convoluted and collecting tubules while also driving potassium excretion into the urine.
Natriuretic peptides. Myocardial natriuretic peptides are released from atrial and ventricular myocardium in response to volume expansion; these inhibit sodium resorption in the distal renal tubules, thus leading to sodium excretion and diuresis. They also induce systemic vasodilation.