Human Physiology, 14th edition (2016)

Cardiac Output, Blood Flow, and Blood Pressure 467

thus promote vasodilation. For example, endothelin-1 recep-

tor antagonists may be used to help treat pulmonary hyperten-

sion. In normal physiology, the effects of endothelin-1 may be

balanced by nitric oxide to help regulate blood flow and blood

pressure.

Intrinsic Regulation of Blood Flow

Intrinsic, or “built-in,” mechanisms within individual organs

provide a localized regulation of vascular resistance and blood

flow. Autoregulation refers to the ability of some organs—

particularly the brain and kidneys—to utilize intrinsic con-

trol mechanisms to maintain a relatively constant blood flow

despite wide fluctuations in blood pressure. Intrinsic mecha-

nisms are classified as myogenic or metabolic.

Myogenic Control Mechanisms

If the arterial blood pressure and flow through an organ are

inadequate—if the organ is inadequately perfused with blood—

the metabolism of the organ cannot be maintained beyond a

limited time period. However, excessively high blood pressure

can also be dangerous, particularly in the brain, because this

may result in the rupture of fine blood vessels (causing a cere-

brovascular accident—CVA, or stroke).

Autoregulation of blood flow helps to mitigate these possibil-

ities. Changes in systemic arterial pressure are compensated for

oxide (NO) from L-arginine. The NO diffuses into the smooth
muscle cells of the tunica media of arterioles and activates the
enzyme guanylate cyclase, which converts GTP into cyclic
GMP (cGMP) and pyrophosphate (PP i ). The cGMP serves as a
second messenger that, through a variety of mechanisms, low-
ers the cytoplasmic Ca^2 1 concentration. This leads to smooth
muscle relaxation and thus to vasodilation (see chapter 20,
fig. 20.21).
Many scientists believe that nitric oxide, in addition to
functioning as a paracrine regulator within the vessel wall
where it is produced, also functions as a hormone carried by
the blood to distant vessels. Nitric oxide can bind to the sul-
fur atoms of cysteine amino acids within hemoglobin (forming
S-nitrosohemoglobin, abbreviated SNO ), which may then trans-
port the nitric oxide in the blood downstream to vessels of other
organs. The binding of nitric oxide to the cysteines in hemoglo-
bin is favored by high oxygen concentrations, and the release of
nitric oxide—producing vasodilation and thus increased blood
flow—is favored by low oxygen concentrations. However,
the physiological significance of this effect is not yet firmly
established.
The endothelium also produces paracrine regulators that
promote vasoconstriction. Notable among these is the polypep-
tide endothelin-1. This paracrine regulator stimulates vasocon-
striction of arterioles, thus raising the total peripheral resistance.
Endothelin-1 receptor antagonists are now medically avail-
able to block the vasoconstrictor effect of endothelin-1, and

Table 14.4 | Extrinsic Control of Vascular Resistance and Blood Flow

Extrinsic Agent Effect Comments

Sympathetic nerves

Alpha-adrenergic Vasoconstriction Vasoconstriction is the dominant effect of sympathetic nerve stimulation on the

vascular system, and it occurs throughout the body.

Beta-adrenergic Vasodilation There is some activity in arterioles in skeletal muscles and in coronary vessels, but

effects are masked by dominant alpha-receptor-mediated constriction.

Cholinergic Vasodilation Effects are localized to arterioles in skeletal muscles and are produced only during

defense (fight-or-flight) reactions.

Parasympathetic nerves Vasodilation Effects are restricted primarily to the gastrointestinal tract, external genitalia, and

salivary glands and have little effect on total peripheral resistance.

Angiotensin II Vasoconstriction A powerful vasoconstrictor produced as a result of secretion of renin from the kidneys;

it may function to help maintain adequate filtration pressure in the kidneys when

systemic blood flow and pressure are reduced.

ADH (vasopressin) Vasoconstriction Although the effects of this hormone on vascular resistance and blood pressure in

anesthetized animals are well documented, the importance of these effects in

conscious humans is controversial.

Histamine Vasodilation Histamine promotes localized vasodilation during inflammation and allergic reactions.

Bradykinins Vasodilation Bradykinins are polypeptides secreted by sweat glands and by the endothelium of

blood vessels; they promote local vasodilation.

Prostaglandins Vasodilation or

vasoconstriction

Prostaglandins are cyclic fatty acids that can be produced by most tissues, including

blood vessel walls. Prostaglandin I 2 is a vasodilator, whereas thromboxane A 2

is a vasoconstrictor. The physiological significance of these effects is presently

controversial.