In healthy arterial walls, the overall indirect relaxation induced by acetylcholine (via nitric oxide) is of greater effect than any contraction that is induced. When the endothelium is dysfunctional, stimulation with acetylcholine will fail to produce, or produce very little, nitric oxide. Thus, acetylcholine released by the PSNS at rest will simply cause contraction of the vascular smooth muscle. Thromboxane A2, serotonin, histamine, and endothelin are vasoconstrictor which activated platelets release and/or cause to be released. Abnormal platelet activation (e.g. by lipoprotein(a) interference with fibrinolysis by competing with plasminogen to thereby impair fibrinolysis and promote platelet activation) results in the release of these mediators and coronary vasospasm. Increased alpha-adrenergic receptor activity in epicardial coronary arteries or the excessive release of the "flight or fight" catecholamines (e.g. norepinephrine) that activate these receptors may lead to coronary vasospasm.Other factors thought to be associated with the development of variant angina include: intrinsic hypercontractility of coronary artery smooth muscle; existence of significant atherosclerotic coronary artery disease; and reduced activity of the parasympathetic nervous system (which normally functions to dilate blood vessels). Diagnosis
Although variant angina has been documented in between 2% to 10% of angina patients, it can be overlooked by cardiologists who stop further evaluations after ruling out typical angina. Individuals who develop cardiac chest pain are generally treated empirically as an "acute coronary syndrome", and are immediately tested for elevations in their blood levels of enzymes such as creatine kinase isoenzymes or troponin that are markers for cardiac damage.
Blood tests
Serum ferritin and fasting transferrin saturation are commonly used as screening for haemochromatosis. Transferrin binds iron and is responsible for iron transport in the blood. Measuring ferritin provides a crude measure of iron stores in the body. Fasting transferrin saturation values in excess of 45%, and the serum ferritin more than 250 ug/L in males and 200 ug/L in females are recognized as a threshold for further evaluation of haemochromatosis. Other source says that the normal values for males are 12-300 ng/mL and for female, 12-150 ng/mL. Fasting transferrin saturation is a better test to detect HH. Transferrin saturation greater than 62% is suggestive of homozygosity for mutations in the HFE gene.Ferritin, a protein synthesized by the liver, is the primary form of iron storage within cells and tissues. Measuring ferritin provides a crude estimate of whole-body iron stores, though many conditions, particularly inflammatory conditions, infection, chronic alcohol consumption (mainly >20g/day), liver disease, cancer, porphyria, Hemophagocytic lymphohistiocytosis, hyperthyroidism, obesity, metabolic syndrome, diabetes, several blood transfusions, too many iron supplements, aceruloplasminemia, atransferrinemia, hyperferritinemia cataract syndrome and others, can elevate serum ferritin, which can account for up to 90% of cases where elevated levels are observed. Measuring iron in the body</ref> Serum ferritin in excess of 1000 ng/mL of blood is almost always attributable to haemochromatosis.Other blood tests routinely performed include blood count, renal function, liver enzymes, electrolytes, and glucose (and/or an oral glucose tolerance test). Liver biopsy
Liver biopsies involve taking a sample of tissue from the liver, using a thin needle.