[Cardiodepressive effects of muscular exercise in spontaneously hypertensive rats]. / Effetti cardiodepressivi dell'esercizio muscolare in ratti spontaneamente ipertesi.

Conflicting results have been reported on the differences in the cardiovascular reactivity to muscular exercise between normotensive and hypertensive subjects and normotensive subjects with family history of hypertension and normotensive subjects without familial hypertensive history. Also studies performed in spontaneously hypertensive in comparison with normotensive rats have not led to final conclusions. Therefore, the aim of the present study was twofold: to evaluate cardiorespiratory reactivity to different types of muscular exercise in normotensive (WKY) compared to spontaneously hypertensive rats (SHR) at pre-hypertensive and hypertensive stages; to verify the role played by the "muscular reflex drive" in mediating the cardiorespiratory responses in rats. We utilized four groups of anesthetized rats: 8 young WKY, 8 SHR in pre-hypertensive stage, 6 adult WKY and 6 SHR in hypertensive stage. We evaluated the cardiorespiratory responses to (rhythmic) dynamic and (static) isometric contractions of gastrocnemius muscles induced by electrical stimulation of the tibial nerve. Cardiorespiratory responses during the initial phase of dynamic and static contractions of hindlimb muscles were studied. Muscle contractions were elicited by stimulating the tibial nerves at 3 and 100 Hz. We measured: mean arterial pressure (MAP), heart rate (HR), and pulmonary ventilation (VE). Both types of exercise caused a significant decrease in MAP and a significant increase in VE while HR did not change significantly. The four groups of rats did not show significant differences in the pattern of cardiorespiratory responses to muscular exercise. The cardiorespiratory reflexes initiated by activation of muscle receptors, verified by interrupting the afferents from the contracting muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of alpha-human atrial natriuretic peptide in guinea-pig isolated heart.

The aim of the present investigation has been to ascertain whether or not atrial natriuretic peptides (ANP) can exert a direct effect on myocardial contractility. Alpha-human ANP (alpha-hANP) concentrations ranging from 1 pM to 50 nM have been used to perfuse guinea-pig isolated hearts in a non-recirculating Langendorff apparatus. A dual concentration-related effect has been induced by alpha-hANP on myocardial function. A maximal increase of +LV dP/dtmax (+56%; P < 0.001) has been observed when guinea-pig hearts were perfused with 100 pM alpha-hANP, whereas a 25% decrease (P < 0.01) occurred with 50 nM alpha-hANP. Similar effects have also been induced by alpha-hANP on the coronary flow rate (CFR). A significant CFR increase (maximal at 10 pM alpha-hANP) was induced by picomolar concentrations of alpha-hANP, whereas a progressive decrease, which was maximal (-28%; P < 0.01) at 50 nM alpha-hANP, was observed with nanomolar concentrations of the peptide. No effects have been observed on heart rate. These results suggest that ANP has direct effects on both vascular and myocardial muscle cells. Coronary vasoconstriction induced by nanomolar concentrations of ANP can contribute to the cardiodepression, whereas ANP in picomolar concentrations can induce a coronary vasodilation which is not coupled with the enhanced myocardial contractility. The latter is the likely expression of a direct effect of the peptide on myocardial function.

[The physiopathological aspects and new therapeutic approaches in cardiac-circulatory failure]. / Aspetti fisiopatologici e nuovi indirizzi terapeutici nell'insufficienza cardio-circolatoria.

Pathophysiological mechanisms are reviewed concerning the onset and the perpetuation of the clinical features of congestive heart failure. This syndrome is a severe condition of poor prognosis and bad life quality which in the last decades has reached, in the western industrial countries, the highest levels of general mortality, mainly due to the high prevalence of hypertensive and ischaemic myocardiopathies in the last years. To the clinical features of heart failure mainly contributes a deregulation of the physiological compensatory mechanisms contemporarily and concurrently activated following the primary deficiency of the heart pump function. In physiological conditions, following the myogenic adapting mechanisms reflex mechanisms intervene, activated by intracardiac and aortic and carotid-sinus mechanoreceptors following the variations in intracardiac and intravascular pressure and generally evoking negative feed-back effects. In patients with heart failure arterial high pressure mechanoreceptors respond to the reduction in effective arterial pressure thus provoking a deactivation of the tonic inhibition on the sympathetic cardiovascular drive. This leads to an activation of peripheral and renal vasoconstrictor tone, to a raised medullary catecholamine incretion, to heart rate and inotropism stimulation, and to an increase in pituitary gland ADH production as well as to an activation of renin-angiotensin-aldosterone system (RAAS). Analogous vasoconstrictive, and sodium and water retentive effects can be elicited by endothelin produced by endothelial cells and found in high plasma levels in CHF. These excitatory effects, leading to a rise in systemic vascular resistance and to hydro-electrolytic retention with volume expansion, are not efficiently counteracted by the opposite effects triggered by cardiopulmonary vagally mediated mechanoreceptors activated by the raised cardiac filling pressure and leading to sympathetic nervous inhibition, peripheral and renal vasodilation, ADH and RAAS inhibition. Analogous effects should be provoked by the raised production, due to enhanced heart wall distension, of atrial natriuretic factor leading to vasodilation, natriuresis and diuresis. Reduced sensitivity of cardiopulmonary baroreceptors and lowered production of ANF due to structural cardiac changes could represent, according to most opinions, the main factors responsible for the prevailing sympathetic activation and hydro-saline retention in CHF. The activation of cardiopulmonary sympathetic positive-feed back afferents, could be also involved in the characteristic alteration of the vago-sympathetic balance in heart failure. The persistent reduction in heart pump function could lead to the instauration of vicious circles among the various regulatory systems and create an overcompensation condition.(ABSTRACT TRUNCATED AT 400 WORDS)

[Integrated cardiorespiratory changes induced by chemical stimulation of muscular receptors]. / Modificazioni integrate cardiorespiratorie indotte da stimolazione chimica di recettori muscolari.

Muscular exercise is accompanied by evident and perfectly matched cardiovascular and respiratory adjustments to avoid changes in arterial blood gases. The mechanisms responsible for this perfect regulation have not yet been defined. Our previous experimental investigations have shown that a consistent rate of cardiorespiratory reflex responses to exercise is caused by chemosensitive muscular receptors activation. The 2 different types of classical muscular exercise (rhythmic and isometric exercise) are joined with the 2 different patterns of cardiorespiratory reflex responses attributed in our opinion to the activation of 2 different kinds of muscle receptors (K and P). It has been observed that the increase in ventilation (VE), elicited by activation of both types of chemoreceptors during muscular experimental exercise is not accompanied by significant variations of partial pressure of CO2 (PaCO2) in the arterial blood (isocapnic hyperpnea). This suggest that muscular chemoreceptor activation during physical exercise determines an adequate cardiopulmonary matching. The main purpose of the present study has been to verify, in anesthetized rabbits, if also the chemical activation of muscular receptors was able to evoke reflexly an adequate degree of cardiopulmonary matching. The ventilation reflex changes and the concomitant variations of PaCO2 induced by injection of bradikinin (BK 250 ng) and hypertonic solutions (NaCl 10% 1 ml) in femoral artery have been evaluated in 10 anesthetized rabbits. The PaCO2 modifications observed during reflex hyperpnea have been compared with those recorded during hyperpnea induced by artificial ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Study of the interactions of atrial natriuretic peptides with the autonomic nervous system. Effects on cardiocirculatory and respiratory reflexes caused by activation of chemosensitive muscle receptors]. / Studio delle interazioni dei peptidi natriuretici atriali con il sistema nervoso autonomo. Effetti sui riflessi cardiocircolatori e respiratori da attivazione di recettori chemosensibili muscolari.

In order to verify the hypothesis that possible interactions with the autonomic nervous system may contribute to the cardiovascular effects of atrial natriuretic factor (ANF), 9 rabbits were anesthetized to study the effect of the infusion of synthetic human ANP (2 mcg/kg in bolus followed by 0.2 mcg/kg/min for 20 min iv) on the reflex responses induced by intra-arterially injected BK (250 ng) and hypertonic NaCl (10%) or glucose (40%). The infusion of ANP provoked a decrease in systolic (SBP, 14%) and diastolic (DBP, 8%) pressure without any significant changes in heart rate (HR). The injection of BK and hypertonic NaCl into femoral arteries carried out during ANP infusion produced cardiorespiratory response patterns similar to those observed in control conditions. After injecting BK, a fall in SBP (25%), DBP (50%) and HR (16%), and an increase in breathing frequency were observed. After injecting NaCl, an increase occurred in SBP (20%), DBP (25%), HR (10%) and in depth of breathing. In the present experimental conditions, ANP has not been found to be capable of significantly interfering with the reflex pattern of cardiorespiratory responses either from the inhibition or activation of the sympathetic nervous system induced by chemical stimulation of muscle receptors.