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The measurement of immunoreactive "angiotensin II” in plasma cannot provide an accurate reflection of the efficacy of angiotensin-converting enzyme (ACE) inhibition because different angiotensin fragments interfere in all radioimmunoassays available so far. More complex methods are necessary in order to measure specifically angiotensin-(1-8)octapeptide. With such methodology it can be shown that no tolerance develops to the angiotensin II-reducing effect of ACE inhibitors after prolonged administration. Marked reduction of angiotensin II levels can be shown even in patients with primary aldosteronism. At peak blockade, the level of plasma angiotensin II is still related to circulating active renin and angiotensin I. Accordingly, because ACE inhibitors raise circulating angiotensin I in a dose-dependent fashion, this should be taken into account when dosing ACE inhibitors. The hypothesis that tissue renin-angiotensin systems play an important independent role in determining vasomotor tone is very interesting. However, any discussion on whether tissue or plasma renin determines the pharmacological effect of ACE inhibitors should be based on the simultaneous measurement of true angiotensin II in tissue and plasma under steady-state conditions. Am J Hypertens 1989;2:286-293

BACKGROUND: The activity of the renin-angiotensin system is usually evaluated as plasma renin activity (PRA, ngAI/ml per h) but the reproducibility of this enzymatic assay is notoriously scarce. We compared the inter and intralaboratory reproducibilities of PRA with those of a new automated chemiluminescent assay, which allows the direct quantification of immunoreactive renin [chemiluminescent immunoreactive renin (CLIR), microU/ml]. METHODS: Aliquots from six pool plasmas of patients with very low to very high PRA levels were measured in 12 centres with both the enzymatic and the direct assays. The same methods were applied to three control plasma preparations with known renin content. RESULTS: In pool plasmas, mean PRA values ranged from 0.14 +/- 0.08 to 18.9 +/- 4.1 ngAI/ml per h, whereas those of CLIR ranged from 4.2 +/- 1.7 to 436 +/- 47 microU/ml. In control plasmas, mean values of PRA and of CLIR were always within the expected range. Overall, there was a significant correlation between the two methods (r = 0.73, P < 0.01). Similar correlations were found in plasmas subdivided in those with low, intermediate and high PRA. However, the coefficients of variation among laboratories found for PRA were always higher than those of CLIR, ranging from 59.4 to 17.1% for PRA, and from 41.0 to 10.7% for CLIR (P < 0.01). Also, the mean intralaboratory variability was higher for PRA than for CLIR, being respectively, 8.5 and 4.5% (P < 0.01). CONCLUSION: The measurement of renin with the chemiluminescent method is a reliable alternative to PRA, having the advantage of a superior inter and intralaboratory reproducibility.

But de l’étude. – L’innervation autonome du coeur est composée de fibres nerveuses des systèmes sympathique et parasympathique, et duplexus ganglionnaire intrinsèque. La neurotransmission intracardiaque par la noradrénaline ou l’acétylcholine est accompagnée d’une libération deneuropeptides avec un effet modulateur. La co-expression de l’angiotensine II dans les fibres sympathiques noradrénergiques et son rôle biologiquedans le coeur humain sont inconnus jusqu’à présent. Méthodes. – Des échantillons de coeurs humains (n = 3, autopsie clinique) ont été étudiés par méthode immunocytologique sur des coupestissulaires effectuées au cryostat. La présence intraneuronale de l’angiotensine II a été dépistée à l’aide de l’anticorps monoclonal 4B3 de souris.La co-expression simultanée de la tyrosine hydroxylase, marqueur catécholaminergique, a été étudiée par des anticorps polyclonaux de lapins. Lavisualisation était par microscopie confocale ou à balayage laser. Résultats. – Des fibres autonomes angiotensinergiques sans ou avec un cophénotype catécholaminergique ont été dépistées dans toutes les partiesdes ventricules. Elles étaient regroupées dans des faisceaux comptant jusqu’à plusieurs dizaines de fibres et suivaient les septums anatomiquespréformés et les vaisseaux épicardiques avant de se distribuer dans le myocarde et l’endocarde. Ces fibres étaient en règle générale sans élargissementssynaptiques ou n’en montraient que quelques aux terminaisons (fibres catécholaminergiques). Les fibres exclusivement hydroxylase-positivesmontraient typiquement des synapses multiples enfilées. Conclusion. – Les fibres autonomes du coeur humain comportent des fibres angiotensinergiques avec un cophénotype sympathique efférent etdes fibres exclusivement angiotensinergiques probablement d’origine sensible. La neurotransmission angiotensinergique pourrait jouer un rôle demodulateur indépendant de l’activité des systèmes sympathique et parasympathique cardiaques.© 2015 Elsevier Masson SAS. Tous droits réservés.Mots, AIM The autonomic innervation of the heart consists of sympathetic and parasympathetic nerve fibres, and fibres of the intrinsic ganglionated plexus with noradrenaline and acytylcholine as principal neurotransmitters. The fibres co-release neuropeptides to modulate intracardiac neurotransmission by specific presynaptic and postsynaptic receptors. The coexpression of angiotensin II in sympathetic fibres of the human heart and its role are not known so far. METHODS Autopsy specimens of human hearts were studied (n=3; ventricles). Using immunocytological methods, cryostat sections were stained by a murine monoclonal antibody (4B3) directed against angiotensin II and co-stained by polyclonal antibodies against tyrosine hydroxylase, a catecholaminergic marker. Visualisation of the antibodies was by confocal light microscopy or laser scanning microscopy. RESULTS Angiotensin II-positive autonomic fibres with and without a catecholaminergic cophenotype (hydroxylase-positive) were found in all parts of the human ventricles. In the epicardium, the fibres were grouped in larger bundles of up to 100 and more fibres. They followed the preformed anatomic septa and epicardial vessels towards the myocardium and endocardium where the bundles dissolved and the individual fibres spread between myocytes and within the endocardium. Generally, angiotensinergic fibres showed no synaptic enlargements or only a few if they were also catecholaminergic. The exclusively catechalominergic fibres were characterised by multiple beaded synapses. CONCLUSION The autonomic innervation of the human heart contains angiotensinergic fibres with a sympathetic efferent phenotype and exclusively angiotensinergic fibers representing probably afferents. Angiotensinergic neurotransmission may modulate intracardiac sympathetic and parasympathetic activity and thereby influence cardiac and circulatory function.

Fermentation of milk by the Lactobacillus helveticus LBK-16H or hydrolysis of casein by protease of Aspergillus oryzae generates the tripeptide casokinines Val-Pro-Pro and Ile-Pro-Pro. These peptides inhibit the kininase II (also known as Angiotensin Converting Enzyme, ACE). Daily intake of these peptides in sufficient amounts in milk, fruit vegetable drinks or pills slightly decreases the blood pressure in hypertensive patients. The currently available milk peptides decrease the blood pressure clearly less than the antihypertensive drugs. They can therefore merely be used for concomitant and safe lifestyle modification during prevention and therapy of hypertension.