Ion Haulica

Angiotensin peptides and their pleiotropic actions

The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has emerged that angiotensin II (Ang II) is not the only biologically active peptide generated by the RAS. At least three others have been identified: the heptapeptide Ang III, the hexapeptide Ang IV and Ang 1-7. Specific receptors exits for the last two peptides. In addition, the range of possible physiological and pathophysiological properties for Ang II„ has been expanding. The current perception of the RAS is therefore that of a much more complex system than previously believed, with autocrine, paracrine and endocrine properties extending beyond the cardiovascular system. This mini-review focuses on the synthetic pathways of the Ang peptides and describes some of their pleiotropic actions.

Biphasic effects of angiotensin (1-7) and its interactions with angiotensin II in rat aorta

Using isolated rat aortic rings perfused with Krebs-Henseleit saline, the vascular effects of angiotensin (1-7) (Ang [1-7]) and its interactions with angiotensin II (Ang II) were investigated. Ang (1-7) induced endothelium-dependent relaxation and vasodilating effects in preparations precontracted with phenylephrine. Without preconstriction, Ang (1-7) at high doses (10 -6—10-5 M) produced either a significant inhibition of Ang IIinduced vasoconstriction or a non-tachyphylactic vasopressor response. While losartan inhibited the vasoconstriction induced by Ang (1-7), A779 blocked only its relaxation. Unlike losartan, blockade of AT2-receptors with PD 123319 had no effect. Taking into account the biphasic effects of angiotensin (1-7), we propose that it is one of the active components of the renin-angiotensin system, which is involved as a modulator both in the counter-regulatory actions of Ang II and in the self-regulation of its own vasodilating effects.

Aspects Regarding the Neurobiology of Psycho-Affective Functions

Aspects Regarding the Neurobiology of Psycho-Affective Functions In this mini-review we were interested in analyzing the main achievements concerning the neurobiological substrate of the human psycho-affective functions. The cortico-subcortical areas implicated in the elaboration and the control of the sensorial and psycho-affective reactions of the human brain are described, as well as the neurobiological basis of the psychic and affective manifestations, with focus on the new achievements in understanding the genetic, morpho-chemical and electromagnetic bases of the psycho-affective and behavioral manifestations, both normal and pathological. It is known that emotional states like anxiety, fear or anger generate complex psycho-affective reactions that are controlled by the limbic system, which is called the emotional brain. This is connected with the polyneuronal circuits of the Papez loop, the hypothalamic-pituitary complex and the reticular formation of the brainstem. Some imagistic aspects concerning the implication of the amygdala and the cingulate gyrus in laughing and crying are mentioned, as well as the cerebral areas implicated in romantic and maternal love. Also, some electromagnetic manifestations of the brain are presented, introducing the concept of «electromagnetic plasma», as a possible component of the human brain activity. Aspekti Koji se Tiču Neurobiologije Psihičko-Afektivnih Funkcija Naš interes u ovom mini pregledu bio je da analiziramo glavna dostignuća vezana za neurobiološki supstrat humanih psihičko-afektivnih funkcija. Opisana su kortiko-supkortikalna područja uključena u elaboraciju i kontrolu senzornih i psihičko-afektivnih reakcija u ljudskom mozgu, kao i neurobiološka osnova psihičkih i afektivnih manifestacija, uz poseban osvrt na nova dostignuća u razumevanju genetskih, morfo-hemijskih i elektromagnetskih osnova psihičko-afektivnih i bihevioralnih manifestacija, kako normalnih, tako i patoloških. Poznato je da emocionalna stanja poput anksioznosti, straha ili besa stvaraju složene psihičkoafektivne reakcije koje kontroliše limbički sistem, koji se još naziva emocionalnim mozgom. Ovo je povezano s polineuronalnim kolima Papezovog kruga, kompleksom hipotalamus-hipofiza i retikularnom formacijom moždanog stabla. Navedeni su neki aspekti slikovne dijagnostike koji se tiču učešća amigdale i gyrus cingulatus-a u smejanju i plakanju, kao i cerebralnih područja koja imaju ulogu u romantičnoj i majčinskoj Ijubavi. Takođe su predstavljene neke elektromagnetske manifestacije mozga, uz uvođenje koncepta «elektromagnetske plazme», kao moguće komponente aktivnosti Ijudskog mozga.

P02-170 Comparative effects of captopril, losartan and PD123319 on the memory processes in rats

Aims Renin-angiotensin system in the central nervous system participates in the processing of sensory information, learning and memory processes. Inhibitors of renin-angiotensin system, particularly angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists are reported to have potential effects in various learning and memory processes. In the present study we assessed the effects of angiotensin converting enzyme inhibitor captopril and the angiotensin AT1 receptors antagonists, lostartan and PD123319, in learning and memory processes by means of Y-maze and passive avoidance tasks. The anxiety state was measured in elevated plus maze. Methods Male Wistar rats were divided into three groups: 1. sham-operated; 2. Captopril; 3. Losartan; 4. PD123319. All drugs were stereotaxically icv injected, rather than captopril (i.p.). Learning and memory tests began 2 weeks after the operation, and the ability of the rats to acquire the operant task was studied by means of Y-maze task and passive avoidance task, respectively. The anxiety state was measured in elevated plus maze. Results Captopril, losartan and PD123319 significantly impaired spatial memory in Y-maze task, suggesting significant effects on short-term memory. In passive avoidance task, all drugs, significantly decreased step-through-latency, suggesting significant effects on long-term memory. In elevated plus maze measuring anxiety, all drugs diminished anxiety state. Conclusions These results suggest the involvement of the brain renin-angiotensin system in learning and memory formation.

Adenosine effects upon the spontaneous quantal transmitter release at the frog neuromuscular junction in the presence of protein kinase C-blocking and -activating agents

This paper gives experimental evidence involving protein kinase C (PKC) in the inhibitory effects of adenosine (ADO) upon the spontaneous transmitter release at the frog neuromuscular junction. In the presence of two PKC inhibitors--polymyxin B (5 x 10(-6) mol/l) and H-7 (10(-5) mol/l), both adenosine (5 x 10(-5) mol/l) and its stable analogue 1-PIA (5 x 10(-8) mol/l), significantly increased the rate of the spontaneous release of acetylcholine quanta. Even when PKC was activated with OAG (5 x 10(-6) mol/l) or TPA (162 x 10(-9) mol/l) and quantal release was increased greatly, ADO still inhibited release. ADO deaminase increased the PKC-induced activation of the transmitter release significantly.

P02-169 Behavioral changes induced by angiotensin AT1 receptors blockade in the rat brain

Aims The brain renin-angiotensin system is involved in learning and memory, but the actual role of angiotensin II and its metabolites in this process has been difficult to comprehend. In the present study we assessed the role of the angiotensin AT1 receptors in certain behavioral effects of angiotensin II using their selective antagonist losartan and PD123319, intracerebroventricularly (icv) administrated. Methods Male Wistar rats were divided into three groups: 1. sham-operated; 2. Losartan; 3. PD123319. All drugs were stereotaxically icv injected. Learning and memory tests began 2 weeks after the operation, and the ability of the rats to acquire the operant task was studied by means of Y-maze task and passive avoidance task, respectively. The anxiety state was measured in elevated plus maze. Results Losartan and PD123319 significantly impaired spatial memory in Y-maze task, suggesting significant effects on short-term memory. In passive avoidance task, both angiotensin II antagonist, significantly decreased step-through-latency, suggesting significant effects on long-term memory. In elevated plus maze measuring anxiety, both drugs diminished anxiety state. Conclusions Our results suggest the considerable involvement of the brain ATi angiotensin receptors in the cognition improving effects of angiotensin.

Comparative study of the inhibitory effects of adrenomedullin on angiotensin II contraction in rat conductance and resistance arteries

Adrenomedullin (ADM), a ubiquitous vasoactive peptide, has been the target of a multitude of studies concerning its effect on the vascular tone. The present work aims at clarifying a series of its interactions with the renin-angiotensin system. The study uses the rat aorta ring as a model of conductance vessels, with or without vascular endothelium, and the second order branch of rat mesenteric arteries as a model of resistance arteries. Interactions between various concentrations of ADM and angiotensin II (Ang II) were studied, in the presence of L-NAME (a nitric oxide [NO] synthase inhibitor) and methylene blue (MB; a soluble guanylate cyclase inhibitor). Results point out differences in the mechanism of the inhibitory action of ADM upon Ang II effects in the two vessel types studied. Inhibition of Ang II contraction by ADM involves guanylate cyclase in both cases. However, NO is involved in ADM-induced inhibition of angiotensinergic not in the resistance ones. vasoconstriction only in the conductance arteries, not in the resistance ones.