This chapter is related to the aims of Section C(iv) from the 2017 CICM Primary Syllabus, which expects the exam candidate to "explain receptor activity with regard to... second messengers and G proteins". Whereas cyclic AMP is probably the stereotypic secondary messenger molecule with importance primarily to catecholamine inotropes, cyclic GMP is the critical molecule required for smooth muscle relaxation.
If your home institution gives you access to archive copies of Pharmacological Reviews, the 1987 article by Waldman and Murad is an excellent and highly detailed introduction to this topic. It is of course well in excess of what is required for the CICM primary exam, in which this topic has never appeared. A more pragmatic article, which happens to be available for free is Tsai & Kass (2009) - this probably has more exam relevance because the focus is on the role of cGMP in regulating cardiovascular phenomena.
- Cyclic guanosine monophosphate is a cyclic nucleotide secondary messenger
- It is produced when guanylyl cyclase is activated by nitric oxide, or by a natriuretic peptide
- It is degraded by phosphodiesterases (some of which also degrade cAMP)
- Its main downstream target is Protein Kinase G (PKG)
- PKG decreases IP3 activity, desensitises myofibrils to calcium, and decreases intracellular calcium availability by several other mechanisms
- The net effect of cGMP secondary messenger activity is smooth muscle relaxation
Cyclic guanosine monophosphate is similar to cyclic AMP, with the exception that instead of adenine cGMP has a guanine nucleobase. It is derived from GTP (guanosine triphosphate). There are two major pathways of its synthesis, one via a membrane-bound guanylyl cyclase bound to a natriuretic peptide receptor, and the other a soluble guanylyl cyclase which is activated by nitric oxide. Like cyclic AMP, cGMP is degraded by phosphodiesterases. Some phosphodiesterases only affect cGMP (eg. PDE-5A, the target of sildenafil) whereas others (PDE-2 and PDE-3) can hydrolyse both cAMP and cGMP.
cGMP has numerous downstream effects, listed nicely in Tsai & Kass (2009):
From Protein Kinase G activation
From cGNP-gated ion channels
From cGMP-modulated phosphodiesterase
In short, the relevance of cGMP to cardiovascular physiology and pharmacology is mainly related to its activation by nitric oxide, and the relevance of this is mainly to vascular smooth muscle. The steps of this activity are as follows:
The net effect of these changes is a decrease in the availability of intracellular calcium, and therefore smooth muscle relaxation.