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.
In addition to their actions on smooth muscle, many vasoactive peptides also function as neurotransmitters and local and systemic hormones. The most important vasoactive peptides include angiotensin, bradykinin, natriuretic peptides, calcitonin gene-related peptide (CGRP), endothelins, 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 17–1Some vasoactive peptides and their properties. |Favorite Table|Download (.pdf) TABLE 17–1 Some vasoactive peptides and their properties.
|Peptide ||Properties |
|Angiotensin II (ANG II) ||↑ 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 |
|Calcitonin gene-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, may play a pathophysiologic role in pulmonary hypertension |
|Neuropeptide Y ||Causes vasoconstriction and stimulates the heart. Effects mediated in part by IP3 |
|Substance P, neurokinins ||Act 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 |
ANGIOTENSIN & ITS ANTAGONISTS
A. Source and Disposition
Angiotensin I is produced from circulating angiotensinogen by renin, an enzyme released from the juxtaglomerular apparatus of the kidney. Angiotensin I is an inactive decapeptide, and is converted into angiotensin II (ANG II, also denoted AII), an active octapeptide, by angiotensin-converting enzyme (ACE), also known as peptidyl dipeptidase or kininase II (see Figure 11–3). Angiotensin II, the active form of the peptide, is rapidly degraded by peptidases (angiotensinases).
B. Effects and Clinical Role