New components and functions of the renin-angiotensin system (RAS) are still being unravelled. The classical RAS as it looked in the middle 1970s consisted of circulating renin, acting on angiotensinogen to produce angiotensin I, which in turn was converted into angiotensin II (Ang II) by angiotensin-converting enzyme (ACE). Ang II, still considered the main effector of RAS was believed to act only as a circulating hormone via angiotensin receptors, AT1 and AT2. Since then, an expanded view of RAS has gradually emerged. Local tissue RAS systems have been identified in most organs. Recently, evidence for an intracellular RAS has been reported. The new expanded view of RAS therefore covers both endocrine, paracrine and intracrine functions. Other peptides of RAS have been shown to have biological actions; angiotensin 2-8 heptapeptide (Ang III) has actions similar to those of Ang II. Further, the angiotensin 3-8 hexapeptide (Ang IV) exerts its actions via insulin-regulated amino peptidase receptors. Finally, angiotensin 1-7 (Ang 1-7) acts via mas receptors. The discovery of another ACE2 was an important complement to this picture. The recent discovery of renin receptors has made our view of RAS unexpectedly complex and multilayered. The importance of RAS in cardiovascular disease has been demonstrated by the clinical benefits of ACE inhibitors and AT1 receptor blockers. Great expectations are now generated by the introduction of renin inhibitors. Indeed, RAS regulates much more and diverse physiological functions than previously believed.

Endothelins (ETs) are the most potent vasoconstrictors known, and may be the mediators of the vasoconstrictive phase in migraine attacks. We studied 31 previously selected migraine patients with (9) and without (22) aura ictally and interictally to determine their plasma ET-1 values. The mean interictal and ictal values were 5.3 pg/ml (SD 1.8) and 6.4 pg/ml (SD 3.9), respectively. The ictal values were markedly elevated at the beginning of the migraine attack (<2 h) and declined to interictal or even lower level later (4 to 6 h) in the course of an attack. The local vasoconstriction at the beginning of a migraine attack might be ET-mediated secondarily to serotonin activation.

Serum and CSF angiotensin converting enzyme (ACE) were measured by a new inhibitor binding assay in 32 patients with sarcoidosis, 49 with neurologic diseases, and 38 controls. In neurosarcoidosis, 11 of 20 patients had high levels of CSF ACE. In systemic sarcoidosis without neurologic abnormality, only 1 of 12 patients had elevated CSF ACE. The highest value was observed in a patient with widespread meningeal sarcoidosis. High values were also observed in patients with bacterial meningitis or malignant tumors of the CNS. Fluctuation in successive analyses correlated to clinical course of neurosarcoidosis. CSF ACE analysis seems useful in diagnosis and follow-up of neurosarcoidosis.

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We describe here a family with autosomal dominant erythrocytosis. In in vitro cultures, performed using the methyl cellulose assay, the number of erythroid colonies was normal or marginally increased when a standard concentration of erythropoietin (Epo) was used, but at lower Epo concentrations, the investigated persons formed more colonies than the controls. The difference was generally greater the lower the Epo concentration became. Some erythroid colony growth was seen even in the absence of any added Epo (apart from the minute concentration found in fetal calf serum), a phenomenon not seen in the controls. This finding indicates that the erythrocytosis in this family is caused by hypersensitivity of erythroid progenitors to Epo. The serum Epo concentration was low or low normal in all of the investigated family members, which is in good accordance with hypersensitivity to Epo. The erythrocytosis has not had any obvious effect on the health or life- span of the affected individuals. Many of them have reached an advanced age, and one of the affected family members has won several Olympic gold medals and world championships in endurance sports.