angiotensin-iii and angiotensin-pentapeptide

The right atrium is densely innervated and provides sensory input to important cardiocirculatory reflexes controlling cardiac output and blood pressure. Its angiotensin (Ang) II-expressing innervation may release Ang II as a neuropeptide cotransmitter to modulate reflexes but has not yet been characterized.. Intraoperative surgical biopsies from human right atria (n = 7) were immunocytologically stained for Ang II, tyrosine hydroxylase (TH), and synaptophysin (SYN). Tissue angiotensins were extracted and quantified by radioimmunoassay.. Angiotensinergic fibers were frequent in epicardial nerves and around vessels with variable TH co-localization (none to >50%/bundle). Fibers were also widely distributed between cardiomyocytes and in the endocardium where they were typically nonvaricose, TH/SYN-negative and usually accompanied by varicose catecholaminergic fibers. In the endocardium, some showed large varicosities and were partially TH or SYN-positive. A few endocardial regions showed scattered nonvaricose Ang fibers ending directly between endothelial cells. Occasional clusters of thin varicose terminals co-localizing SYN or TH were located underneath, or protruded into, the endothelium. Endocardial density of Ang and TH-positive fibers was 30-300 vs. 200-450/mm2. Atrial Ang II, III, and I concentrations were 67, 16, and 5 fmol/g (median) while Ang IV and V were mostly undetectable.. The human right atrium harbors an abundant angiotensinergic innervation and a novel potential source of atrial Ang II. Most peripheral fibers were noncatecholaminergic afferents or preterminal vagal efferents and a minority was presumably sympathetic. Neuronal Ang II release from these fibers may modulate cardiac and circulatory reflexes independently from plasma and tissue Ang II sources.

Topics: Aged; Angiotensin I; Angiotensin II; Angiotensin III; Angiotensins; Autonomic Nervous System; Heart Atria; Humans; Male; Middle Aged; Nerve Fibers; Peptide Fragments; Reflex; Synaptophysin; Tyrosine 3-Monooxygenase

A very reliable isocratic reverse phase high performance liquid chromatography (HPLC) system has been developed to separate angiotensins, which combined with a very sensitive radioimmunoassay, provided precise measurements of the endogenous angiotensin II (AII) concentration in the rat plasma in different experimental circumstances. The overall recoveries of AII were 95.2 +/- 15.8% (means +/- SD) when 10 pg of this peptide was added to 1 ml of human plasma. The coefficient of variation for within-assay precision was 10% (n = 6). The plasma AII, measured by this method, of normal male pentobarbital-anesthetized rats was 53.0-141.6 pg/ml (mean: 103.9 +/- 29.7 pg/ml). The plasma AII of rats fed a sodium deficient diet was 300.0 +/- 100.6 pg/ml, while that of rats given oral Enalapril, an angiotensin converting enzyme (ACE) inhibitor, for 1 week was 35.7 +/- 28.0 pg/ml. The plasma AII of bilaterally nephrectomized rats was 2.7 +/- 2.9 pg/ml 24 hours after nephrectomy and below the detection limit 48 hr after nephrectomy. This method, therefore, can be used to study AII in different pathophysiological states or after treatment with renin-angiotensin system inhibitors.

Topics: Analysis of Variance; Anesthesia; Angiotensin II; Angiotensin III; Angiotensins; Animals; Chromatography, High Pressure Liquid; Enalapril; Male; Osmolar Concentration; Pentobarbital; Peptide Fragments; Radioimmunoassay; Rats; Rats, Inbred Strains; Renin