CV System and Kidney

Whilst the physiologic relevance of copeptin is still unsolved, much is known about the function of AVP. Once released into the circulation, AVP exerts its peripheral effects by binding to tissue-specific G-protein-coupled receptors (GPCR) (see BirnbaumerRef-12 and HolmesRef-13 for details). The two predominant receptors are the V1-receptor, which mediates arteriolar vasoconstriction, and the V2-receptor, which is responsible for the antidiuretic effect in the kidneys. V1-receptors are found in high density on vascular smooth muscle cells and cause vasoconstriction by an increase in intracellular calcium via G-protein-induced inositol triphosphate and diacylglycerol. V1-receptors are also present on cardiac myocytes, but the vasoconstrictive effect on these cells seems to be dose dependent and is still under debate.Ref-13, 14

The V2-receptors are mainly located on the cells of the renal collecting tubules, where they increase intracellular cyclic adenosine monophosphate (cAMP) via the Gs signaling pathway.Ref-12 This increase in cAMP has two effects on water homeostasis: first, it stimulates the synthesis of mRNA encoding aquaporin-2; and second, it increases the traffic of aquaporin-2 vesicles to the apical plasma membrane of the collecting duct, where aquaporin-2 allows the absorption of most of the water present in the urine.

A third AVP receptor, termed the V3-receptor (or V1b-receptor in some literature) seems to be restricted to certain cells of the adenohypophys is and is involved in the secretion of ACTH.Ref-15 Besides the interaction with specific AVP receptors, AVP also binds to the oxytocin receptor with a similar affinity to oxytocin,Ref-16 and to certain purinergic receptors, also members of the GPCR superfamily. Oxytocin receptors are located on the vascular endothelium, where they mediate nitric-oxide-dependent vasodilation.Ref-17 Binding of AVP to these receptors may induce some of the vasodilating effects seen by AVP in certain vascular beds (see HolmesRef-14 for details). AVP interactions with the two latter receptors are also proposed to cause some of the AVP effects on the heart: activation of cardiac oxytocin receptors stimulates the release of atrial natriuretic peptide,Ref-18 whilst stimulation of the P2 class of purinoreceptors of the heart causes coronary vasoconstriction and negative inotropy.Ref-1

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