Somlyo, Andrew P., and Avril V. Somlyo. Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase. Physiol Rev 83: 1325-1358, 2003; 10.1152...

https://www.physiology.org/doi/pdf/10.1152/physrev.00023.2003

Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase

This review discusses the pathogenesis and management of coronary microvascular dysfunction. Factors to consider in clinical management are the cause of the dysfunction and whether it is iatrogenic, whether obstructive coronary artery disease is present, and whether myocardial disease is present.

https://www.nejm.org/doi/suppl/10.1056/NEJMra061889/suppl_file/nejm_camici_830sa1.pdf

Coronary Microvascular Dysfunction

Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. The mammalian members are atrial natriuretic peptide, B-type natriuretic peptide, C-type natriuretic peptide, and possibly osteocrin/musclin. Three single membrane-spanning natriuretic peptide receptors (NPRs) have been identified. Two, NPR-A/GC-A/NPR1 and NPR-B/GC-B/NPR2, are transmembrane guanylyl cyclases, enzymes that catalyze the synthesis of cGMP. One, NPR-C/NPR3, lacks intrinsic enzymatic activity and controls the local concentrations of natriuretic peptides through constitutive receptor-mediated internalization and degradation. Single allele-inactivating mutations in the promoter of human NPR-A are associated with hypertension and heart failure, whereas homozygous inactivating mutations in human NPR-B cause a form of short-limbed dwarfism known as acromesomelic dysplasia type Maroteaux. The physiological effects of natriuretic peptides are elicited through three classes of cGMP binding proteins: cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. In this comprehensive review, the structure, function, regulation, and biological consequences of natriuretic peptides and their associated signaling proteins are described.

/pdf/natriuretic-peptides-their-receptors-and-cyclic-guanosine-mm2sqziu0p.pdf

Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions.

During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. The concentration of this molecule in exhaled air is abnormal in activated states of different inflammatory airway diseases, and its monitoring is potentially a major advance in the management of, e.g., asthma. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response. The fundamental mechanisms driving the altered NO bioactivity under pathological conditions still need to be fully clarified, because their regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways.

/pdf/nitric-oxide-in-health-and-disease-of-the-respiratory-system-3cwysenbku.pdf

Nitric Oxide in Health and Disease of the Respiratory System

https://www.urologic.theclinics.com/article/S0094-0143(05)00079-0/pdf

Physiology of Penile Erection and Pathophysiology of Erectile Dysfunction

Contraction and relaxation of smooth muscle is a tightly regulated process involving numerous endogenous substances and their intracellular second messengers. We examine the key role of cyclic guanosine monophosphate (cGMP) in mediating smooth muscle relaxation. We briefly review the current art regarding cGMP generation and degradation, while focusing on the recent identification of the molecular mechanisms underlying cGMP-mediated smooth muscle relaxation. cGMP-induced SM relaxation is mediated mainly by cGMP-dependent protein kinase activation. It involves several molecular events culminating in a reduction in intracellular Ca(2+) concentration and a decrease in the sensitivity of the contractile system to Ca(2+). We propose that the cGMP-induced decrease in Ca(2+) sensitivity is a strategic way to achieve "active relaxation" of the smooth muscle. In summary, we present compelling evidence supporting a key role for cGMP as a mediator of smooth muscle relaxation in physiological and pharmacological settings.

Molecular mechanism of cGMP-mediated smooth muscle relaxation.

Neuropeptide Y (NPY): a coronary vasoconstrictor and potentiator of catecholamine-induced coronary constriction.

The use of ryanodine and calcium channel blockers to characterize intra- and extracellular calcium pools mobilized by noradrenaline in the rat vas deferens.

J P Huidobro-Toro

Papers

Molecular mechanism of cGMP-mediated smooth muscle relaxation.

Neuropeptide Y (NPY): a coronary vasoconstrictor and potentiator of catecholamine-induced coronary constriction.

The use of ryanodine and calcium channel blockers to characterize intra- and extracellular calcium pools mobilized by noradrenaline in the rat vas deferens.

Role of endothelium-derived relaxing factor on coronary blood flow regulation in the dog.