**Acknowledgements**

*Cardiac Diseases - Novel Aspects of Cardiac Risk, Cardiorenal Pathology and Cardiac Interventions*

1 has also been implicated as a modifier in dilated cardiomyopathy. With variations including the rare G > A and a C > T at c.90 seen in dilated cardiomyopathy patients and *EDN1* polymorphisms linked to increased risk of the disorder, likely by altered the stability of the protein [75]. A model of diabetic cardiomyopathy in rats also showed that plasma endothelin-2 levels were higher that controls and that overex-

Cardiac function is controlled by the SNS and parasympathetic nervous system (PNS). Parasympathetic vagal nerves are distributed throughout all areas of the heart, particularly in the ventricles [77]. Cardiac muscarinic receptors are activated by acetylcholine, having been stimulated by vagal nerve activation. The muscarinic acetylcholine receptors (M-ChR) are glycoproteins belonging to the 7TMR superfamily [77]. The M2 subtype of M-ChR are the most prevalent group within the mammalian heart and their function is opposed to the β-ARs in that they cause a reduction in myocardium contractility and a lower cardiac rate [10]. M-ChR exert their influence on the myocardium via the Gα1-coupled receptors which inhibit adenylyl cyclase whilst the Gβγ dimer impedes the activity of potassium channels in the sinoatrial node [1]. M-ChR can also exert an effect over Ca2+ channels [77]

Heart failure patients demonstrate an increase in M2 muscarinic receptor density, with activated M2 receptors encouraging an inotropic response [9]. One study using serum from a patient showed that when autoantibodies to the muscarinic receptors and β-ARs were activated it resulted in cardiomyopathy and atrial tachyarrhythmias [78]. Along a similar line, autoantibodies against β1-ARs have been shown to cause sudden death in idiopathic dilated cardiomyopathy patients [79]. Antibodies to β-ARs have been discovered in people with idiopathic dilated cardiomyopathy, even leading to the suggestion of a form of 'adrenergic cardiomyopathy' [80]. In addition autoantibodies against muscarinic receptors have also been noted in cases of peripartum cardiomyopathy [81], dilated cardiomyopathy [82–85], and M2-muscarinic acetylcholine receptor autoantibodies have been implicated in playing a role in atrial fibrillation in dilated cardiomyopathy patients [86] Similar increases were not observed in patients with Takotsubo cardiomyopathy [87] or in rats with cirrhotic cardiomyopathy [88]. Autoantibodies against cardiomyocytes, β1- or β2-ARs or M2 muscarinic receptors were not noted in 20 people with Takotsubo cardiomyopathy in comparison to healthy controls, or in

The superfamily of 7TMRs includes receptors for hormones, neurotransmitters and ion channels, and are critical to mediate physiological and cellular processes [1, 2]. This chapter has investigated adrenoreceptors (both α- and β-adrenergic receptors) and the components of the renin-angiotensin system (RAS) especially AngII, ACE and the AT1 and AT2 receptors. The chapter has also looked at endothelin-1 (ET-1) and its receptor, and precursor Big endothelin-1 and finally the muscarinic receptors. By looking at their numerous effects in both healthy and diseased vasculature and cardiac disorders, especially cardiomyopathies, it can be seen that there are wide ranging effects. Developing these 7TMRs as markers of disease, for prognosis, diagnosis and therapeutic treatments is becoming more important as their many roles as being uncovered in the cardiovascular system.

pression of the protein results in a more severe phenotype [76].

**2.4 Muscarinic receptors**

affecting cardiac contractility.

rats with cirrhotic cardiomyopathy.

**3. Conclusions**

**158**

The authors would like to thank their institutions for funding them. Ewelina Prozorowska, Kristýna Glocová, and Lucy Slater were undertaking research internships with Catrin Sian Rutland at The University of Nottingham, UK. Kristýna Glocová had her internship funded by The European Association of Veterinary Anatomists (EAVA), Young Research Career Development Award; therefore, Kristýna and Catrin would like to thank the EAVA. The ORCID ID of Catrin Rutland is https://orcid.org/0000-0002-2009-4898.
