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Home Books Katzung & Trevor's Pharmacology: Examination & Board Review, 10e

Chapter 17. Vasoactive Peptides

Vasoactive peptides are autacoids with significant actions on vascular smooth muscle as well as other tissues. They include vasoconstrictors, vasodilators, and peptides with mixed effects. Antagonists of these peptides or the enzymes that produce them have useful clinical properties.

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In addition to their actions on smooth muscle, vasoactive peptides function as neurotransmitters and local and systemic hormones. The better-known vasoactive peptides include angiotensin, bradykinin, natriuretic peptides, calcitoningene-related peptide (CGRP), endothelin, neuropeptide Y (NPY), substance P and vasoactive intestinal peptide (VIP) (discussed in this chapter), and vasopressin (Chapters 15 and 37). Many other endogenous peptides with very important actions (eg, insulin, glucagon, opioid peptides) have less or no direct vascular smooth muscle effects.

Vasoactive peptides probably all act on cell surface receptors. Most act via G-protein-coupled receptors and cause the production of well-known second messengers (Table 17–1); a few may open ion channels.

Table 17–1 Some Vasoactive Peptides and Their Properties.
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Table 17–1 Some Vasoactive Peptides and Their Properties.
PeptideProperties
Angiotensin II (ANGII)↑ IP3, DAG via AT1 G protein-coupled receptors. Constricts arterioles, increases aldosterone secretion
Bradykinin↑ IP3, DAG, cAMP, NO. Dilates arterioles, increases capillary permeability, stimulates sensory nerve endings
Natriuretic peptides (ANP, BNP)↑ cGMP via ANPA receptors. Dilate vessels, inhibit aldosterone secretion and effects, increase glomerular filtration
Calcitoningene-related peptide (CGRP)An extremely potent vasodilator; causes hypotension and reflex tachycardia
Endothelins↑ IP3, DAG via G protein-coupled ETA and ETB receptors. Synthesized in vascular endothelium. Constrict most vessels and contract other smooth muscle
Neuropeptide YCauses vasoconstriction and stimulates the heart. Effects mediated in part by IP3
Substance P, neurokininsAct on neurokinin receptors (NK1, NK2, NK3). Dilate arterioles, contract veins and intestinal and bronchial smooth muscle, cause diuresis; substance P is a transmitter in sensory pain neurons
Vasoactive intestinal peptide (VIP)↑ cAMP via G protein-coupled receptors VPAC1 and VPAC2. Dilates vessels, relaxes bronchi and intestinal smooth muscle

aANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; DAG, diacylglycerol; IP3, inositol trisphosphate.

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KininsFamily of vasoactive peptides associated with tissue injury and inflammation, for example, bradykinin
Natriuretic peptidesFamily of peptides synthesized in brain, heart, and other tissues; have vasodilator as well as natriuretic effects
NeuropeptidesPeptides with prominent roles as neurotransmitters or modulators; many also have potent smooth muscle effects
PeptidaseFamily of enzymes that activate or inactivate peptides by hydrolysis, for example, angiotensin-converting enzyme (dipeptidyl peptidase), neutral endopeptidase
TachykininsGroup of 3 potent neuropeptides: substance P, neurokinin A, and neurokinin B

Source and Disposition

Angiotensin I is produced from circulating angiotensinogen by renin, an enzyme ...

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