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Biomedical subjects

A Parini

Publications and source records attributed to A Parini.

At least 73 records · Page 4Linked to original sources
PubMed1989

[Interaction of rilmenidine with renal imidazoline-guanidine sites].

Several studies have suggested that clonidine, guanfacine and rilmenidine decrease systemic blood pressure by stimulating central alpha 2-adrenergic receptors. However, we have shown that these molecules interact not only with alpha 2-adrenergic but also a new type of "non catecholamine" receptor in rabbit and human renal proximal tubules. This receptor, which we have called the imidazoline-guanidium receptor site (IGRS) seems to be pharmacologically, biochemically and fractionally distinct from alpha 2-adrenergic receptors. In order to determine the relative affinity of rilmenidine for these two types of receptor, we studied its capacity to inhibit the liaison of (H3)-idazoxan, a ligand with a high affinity for the IGRS, and of (H3)-rauwolscine, a ligand selective for alpha 2-adrenergic receptors in the rabbit kidney. The results based on the apparent constants of inhibition (Ki) of the two radioligands [231 +/- 34 nM for (H3)-idazoxan and 2440 +/- 322 nM for (H3)-rauwolscine] showed that the selectivity of rilmenidine was 10 times greater for IGRS than for alpha 2-adrenergic receptors. This preferential activity on IGRS was confirmed by studies of the influx of Na22 into isolated renal proximal tubule cells of the rabbit. They showed that rilmenidine, in contrast to catecholamines, inhibited the transport of Na22 into the renal cells. In conclusion, the data from our studies shows that rilmenidine interacts with renal IGRS and inhibits cellular transport of sodium by a mechanism other than the stimulation of alpha 2-adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1988

Noradrenaline content and adrenergic receptors in kidney and heart of the prehypertensive and hypertensive Lyon rat strain.

Sympathetic activity modulates the blood pressure in part by activation of cardiac and renal adrenergic receptors. Thus an alteration of tissue noradrenaline content and/or adrenergic receptors in heart and kidney might be involved in the pathogenesis of hypertension. In order to verify this possibility, we studied tissue noradrenaline content and alpha and beta adrenergic receptors in the heart and kidney of Lyon hypertensive (LH), normotensive (LN), and low-pressure (LL) rats. Density and affinity of receptors were determined using the specific radioligands [3H]-prazosin (alpha 1), [3H]-rauwolscine (alpha 2), and [3H]-dihydroalprenolol (beta) in prehypertensive (5-week-old) and hypertensive (21-week-old) rats. In the prehypertensive period, no differences concerning renal and cardiac noradrenaline content and adrenergic receptor densities and affinities were observed. In the hypertensive period, an age-related decrease of renal alpha 1 and beta receptors was observed in LN and LL (P less than 0.01) but not in LH rats. Consequently, at this time, density of renal alpha 1 and beta receptors was higher in LH than in LN and LL (P less than 0.01). In contrast, the density and affinity of renal alpha 2 and cardiac alpha 1 and beta receptors and tissue noradrenaline content were similar in the three rat strains. Because renal alpha 1 and beta receptors mediate various functions involved in the control of blood pressure such as tubular sodium reabsorption, renin secretion, and glomerular filtration, the different density of these receptors in LH rats might be involved in the development or maintenance of hypertension.

Aging↗
PubMed1988

Alpha-adrenoceptors in Dahl hypertensive and normotensive rats: effect of sodium.

Sodium ions play an important role in vitro and in vivo in the regulation of alpha 2-adrenoceptors. The in vitro effect of sodium on cerebral and renal alpha-adrenoceptors was investigated in Dahl salt-sensitive and salt-resistant rats. Cerebral alpha 2-adrenoceptor densities were higher in Dahl salt-resistant rats. In contrast, the renal alpha 2-adrenoceptor density was higher in Dahl salt-sensitive than in Dahl salt-resistant rats. No difference in cerebral and renal alpha 1-adrenoceptor densities was observed between the two types of rat. Noradrenaline contents in the cerebral and renal cortex were also similar in these two rat substrains. An influx of sodium ions markedly increased cerebral and renal high-affinity alpha 2-adrenoceptor densities in Dahl salt-sensitive but not in Dahl salt-resistant rats. Under these conditions alpha 1-adrenoceptor densities remained unchanged. The absence of sodium regulation in Dahl salt-resistant rats may be linked either to a particular receptor conformation or to an abnormal structure of the alpha 2-adrenoceptor system. We conclude from the present study that there are marked differences in density and in the role of sodium regulation of cerebral and renal alpha 2-adrenoceptors from salt-sensitive and salt-resistant Dahl rats. These differences may play a primary role in the resistance or in the sensitivity of salt-induced hypertension.

Animals↗
PubMed1988

Interaction of clonidine and rilmenidine with imidazoline-preferring receptors.

In the present study the imidazoline radioligand 3H-RX 781094 (idazoxan) was used to characterize the alpha 2-adrenergic receptors in basolateral membranes of rabbit proximal tubule. Scatchard analysis of equilibrium binding data showed that 3H-RX 781094 labels 566 +/- 118 fmol/mg protein of binding sites with an apparent dissociation constant (Kd) of 1.45 +/- 0.14 nmol/l. However, in competition studies, only 25% of the 3H-RX 781094 binding was inhibited by catecholamines and alpha 2-adrenergic compounds; the remaining 75% of specific binding was inhibited only by molecules having an imidazoline or oxazoline ring with the following order of potency: cirazoline greater than tolazoline greater than UK 14 304 greater than rilmenidine greater than clonidine. These data suggest that imidazoline compounds bind to both alpha 2-adrenergic receptors and to a 'non-adrenergic site' which might be defined as an imidazoline-preferring receptor. Based on these results, it is possible to hypothesize that imidazoline and oxazoline drugs, such as clonidine and rilmenidine, exert their hypotensive activity partly through the stimulation of imidazoline receptors.

Animals↗
PubMed1988

[Hereditary resistance to salt-induced hypertension. What mechanisms?].

The Sabra hypertension resistant rats (SBN) have an outstanding ability to maintain normal blood pressure when exposed to procedures that ordinarily cause hypertension in normal rats. The following findings may be relevant to resistance to hypertension of these rats: 1) In SBN rats, cardiac norepinephrine content is not affected by DOCA-salt treatment. Since depletion of cardiac norepinephrine is an index of cardiac adrenergic nerve overactivity, the results suggest an attenuated cardiac sympathetic nerve activity in these rats. 2) In SBN rats, the sensitivity of the baroreflex control of the heart is markedly increased compared with other strains. Reduction of baro-receptor sensitivity by aortic-baroreceptor deafferentation renders them susceptible to DOCA-salt hypertension. The results suggest a strong relationship between baroreflex supersensitivity and resistance to hypertension in these rats. 3) The amount of alpha 2 adrenoreceptor densities in cerebral and renal cortical membranes of normal rats increased in vitro, in the presence of sodium and guanyl nucleotide (GTP). In SBN rats, the effect of sodium is markedly attenuated compared with SBH, while response to GTP is identical in the two strains. The demonstration of a similar pattern of response in the Dahl rats suggests that alpha 2 adrenoreceptor may be involved in the sensitivity or resistance to salt induced hypertension.

Animals↗
PubMed1987

Evidence for imidazoline binding sites in basolateral membranes from rabbit kidney.

[3H]-RX 781094 and [3H]-rauwolscine, two potent alpha 2-adrenergic antagonists, were used to characterize alpha 2 receptor in basolateral membranes from rabbit kidney. However, the following findings suggest that the imidazoline [3H]-RX 781094 binds to an heterogeneous population of binding sites: 1) dissociation plot was biphasic with a fast and slow component, 2) in saturation experiments, [3H]-RX 781094 labels 3.5 more binding sites than [3H]-rauwolscine (p less than 0.02), 3) competition studies showed that molecules with imidazoline structure completely inhibited the [3H] RX 781094 binding; in contrast, only 25% of binding was affected by non-imidazoline alpha 2 adrenergic compounds. These results suggest that in basolateral membranes from rabbit kidney, [3H] RX781094 labels alpha 2 adrenergic and non-adrenergic receptors which might be imidazoline-preferring binding sites.

Adrenergic alpha-Antagonists↗
PubMed1987

Selective modification of renal alpha 2-adrenergic receptors in Milan hypertensive rat strain.

Cerebral and renal alpha-adrenergic receptors play an important role in the control of blood pressure. We studied alpha-adrenergic receptors in the cerebral and renal cortex of Milan hypertensive strain (MHS) and normotensive strain (MNS) rats, a genetic model of spontaneous hypertension linked to a kidney abnormality. Binding of the selective alpha 1-adrenergic antagonist [3H]prazosin and the alpha 2-adrenergic antagonist [3H]rauwolscine was used for receptor studies in tissues of prehypertensive (24-day-old) and hypertensive (60-day-old) rats. In the cerebral cortex, no between-strain differences in alpha 1-adrenergic and alpha 2-adrenergic receptor density and affinity were observed in prehypertensive and hypertensive periods. The density of these receptors increased similarly with age in MHS and MNS rats. In the renal cortex, the differences between MHS and MNS rats concerned alpha 2-adrenergic receptors only. Compared with their age-matched normotensive controls, MHS rats showed 1) a lower affinity for the antagonist (p less than 0.05) in the prehypertensive period, 2) absence of the normal age-related increase in receptor density, and 3) a lower density of [3H]rauwolscine binding sites (p less than 0.001) in the hypertensive period. In this period, studies of competitive inhibition of [3H]rauwolscine binding showed that l-epinephrine bound to one class of sites in MHS rats (pseudo-Hill plot, 0.90) and to two classes in MNS rats (pseudo-Hill plot, 0.68). In addition, the lack of any guanylylimidodiphosphate effect on the l-epinephrine competition curve observed in MHS rats suggests the uncoupling of these receptors from the guanosine 5'-triphosphate binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1987

Structural properties of the alpha 1-adrenergic receptor: studies with membrane and purified receptor preparations.

The contribution of hydrophobic, ionic, and disulfide bonds in the alpha 1-adrenergic receptor structure was evaluated using rat hepatic plasma membrane and purified receptor preparations. In addition, the findings were compared with similar structural evaluations of the beta 2-adrenergic receptor purified from canine lung. Both the alpha 1- and beta 2-adrenergic receptors contain a disulfide bond critical for ligand binding. However, the disulfide bond in the beta-receptor structure is accessible to solvent, while the disulfide bond within the alpha-receptor structure is "masked" and inaccessible to solvent. Reduction of this disulfide bond requires initial denaturation of the alpha 1-receptor. Although the tertiary structures of both receptor proteins appear to be stabilized by strong hydrophobic interactions, differential sensitivities are observed with a variety of structural perturbants, including high concentrations of sodium chloride, guanidine hydrochloride, and ethylene glycol.

Animals↗
PubMed1986

Changes in central alpha-adrenoceptors and noradrenaline content after high sodium intake in Sabra salt-sensitive and salt-resistant rats.

Several studies have suggested a correlation between sodium accumulation and the development of hypertension. However, the mechanisms whereby sodium is able to increase blood pressure remain unclear. In the present study, alpha-adrenoceptors and noradrenaline contents have been studied in the cerebral cortex, hypothalamus and medulla oblongata in the Sabra rat strain in order to define their role in the resistance or sensitivity to sodium-induced hypertension. Alpha-Adrenoceptors were defined using the selective ligands 3H-prazosin and 3H-rauwolscine for alpha 1- and alpha 2-adrenoceptors, respectively. Under normal sodium diet, alpha 2-adrenoceptor density was higher in cerebral cortex and lower in hypothalamus and medulla oblongata of SBN (salt-resistant) compared to SBH (salt-sensitive) rats. Five weeks of high sodium intake induced a decrease in alpha 2-adrenoceptor density in cerebral cortex and an increase in hypothalamus only in SBN rats. These changes abolished the differences between SBH and SBN rats observed with a normal sodium diet. No changes in density and affinity of alpha 2-adrenoceptors were observed in medulla oblongata of SBN and SBH rats. Density and affinity of alpha 1-adrenoceptors were similar in SBN and SBH rats in all the tissues studied and they were unaffected by the high sodium diet. Noradrenaline contents in cerebral cortex, hypothalamus and medulla oblongata were also similar in the two rat substrains under normal sodium diet, but high sodium intake induced a decrease cerebrocortical noradrenaline content only in SBN rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Sabra rats as a model to differentiate between Na+ and GTP regulation of alpha 2-adrenoceptor densities.

Sodium ions and guanyl nucleotides play an important role in increasing alpha 2-adrenoceptor densities in cerebral and renal cortex of normotensive rats. The in vitro effect of Na+ and GTP was investigated on cerebral and renal alpha-adrenoceptors in hypertensive (SBH, salt-sensitive) and normotensive (SBN, salt-resistant) Sabra rats. In SBH and SBN rats, guanyl nucleotides increased cerebral and renal high-affinity alpha 2-adrenoceptor densities. Sodium ions, in contrast, markedly increased cerebral and renal high affinity alpha 2-adrenoceptor densities only in SBH rats. Under these conditions, alpha 1-adrenoceptor densities were unchanged. Thus, although Na+ and GTP both increase alpha 2-adrenoceptor densities, these agents appear to mediate their regulatory effects via different membrane components. Moreover, the absence of sodium regulation of alpha 2-adrenoceptors in SBN rats may be responsible for the resistance to salt-induced hypertension.

Animals↗
PubMed1984

[Central alpha 2-adrenergic receptors in the rat: effect of sodium in vitro].

Characteristics of the (3H) Rauwolscine binding were studied in homogenates of rat cerebral cortex, particularly in presence of NaCl. We had shown that (3H) Rauwolscine specifically bind the alpha 2-adrenoceptors. The Scatchard plot analysis had demonstrated 2 sites: a high affinity site (B 41,06 +/- 5,21 KD = 1,31 +/- 0,16) and a low affinity site (B = 203,41 +/- 13,37 KD = 11,62 +/- 0,55 nM). Incubation of cerebral cortex homogenates with NaCl 150 mM induced an increase (53,97 p less than 0.001) of the high affinity site density. These results indicate that (3H) Rauwolscine is a useful alpha 2-adrenoceptor ligand to study in animal models various central nervous system abnormalities or diseases induced by ion disorders.

Animals↗
PubMed1984

Cerebral and renal alpha-adrenoceptors in Sabra hypertensive (SBH) and normotensive (SBN) rats: effects of high-sodium diet.

The aim of the present study was to investigate the effect of high (8%) versus normal (0.2%) sodium diet on cerebral and renal alpha-adrenoceptors of Sabra hypertensive (SBH) and normotensive (SBN) rats. Cerebral alpha 2-adrenoceptor densities were higher in SBN than in SBH rats. In contrast, renal alpha 2-adrenoceptor density was higher in SBH than in SBN rats. No difference in alpha 1-adrenoceptor densities was observed between the two strains. After 2 and 5 weeks of high-sodium diet, alpha 2-adrenoceptor densities were increased in renal cortex of SBH and SBN rats. In contrast, cerebral alpha 2-adrenoceptor densities were markedly decreased in SBN but not in SBH rats. alpha 1-Adrenoceptor densities were unchanged by high salt intake. Blood pressure increased only after 5 weeks of high-sodium diet, markedly in SBH and to a lesser extent in SBN rats. The variation in alpha 2-adrenoceptor densities thus preceded the blood pressure elevation. The dietary sodium-induced increase in renal alpha 2-adrenoceptor densities observed both in SBH and SBN rats does not appear to be a genetic marker of hypertension. In contrast, the marked decrease in cerebral alpha 2-adrenoceptors in SBN rats may represent an adaptative change in sympathetic activity responsible for the resistance to the development of salt-induced hypertension.

Animals↗
PubMed1984

Dietary sodium regulation of alpha 2-adrenoceptors in Sabra hypertensive (SHB) and normotensive (SBN) rats.

Cerebral and renal alpha 2-adrenoceptors, modulated in vitro by sodium ions, are implicated in the control of sympathetic activity and of sodium reabsorption, respectively. The aim of the present study was to investigate the effect of high (8%) versus normal (0.2%) sodium diet on cerebral and renal alpha-adrenoceptors of Sabra hypertensive (SBH) and normotensive (SBN) rats. After two or five weeks of high sodium diet alpha 2-adrenoceptor density was increased in the renal cortex of SHB and SBN rats. In contrast, cerebral alpha 2-adrenoceptor densities were markedly decreased in SBN but unchanged in SBH rats. Blood pressure increased only after five weeks of high sodium diet, in SBH and to a lesser extent in SBN rats. The change in alpha 2-adrenoceptor densities thus preceded the blood pressure elevation. The dietary sodium-induced increase in renal alpha 2-adrenoceptor densities which precedes the blood pressure elevation does not appear to be a genetic marker of hypertension. Conversely, the marked decrease of cerebral alpha 2-adrenoceptors in SBN rats may represent an adaptative change in sympathetic activity responsible for the resistance to the development of salt-induced hypertension.

Animals↗
PubMed1983

Insulin degradation in human erythrocytes. Effect of triton X-100 treatment on insulin-degrading activity of membranes.

Human erythrocyte membrane has been demonstrate to possess an insulin-degrading activity. This activity is not due to a contamination by cytosolic factors and seems to be specific toward insulin. The fractionation of the erythrocyte membrane by Triton X-100 leads to the appraisal of an insulin-degrading activity in the Triton-extracted membranes higher than that present in the solubilized protein fraction. The degrading activity found in the extracted membranes is inhibited by the addition of the solubilized material. This last fraction seems to modulate, in the intact membrane, the whole insulin-degrading system.

Erythrocyte Membrane↗
PubMed1982

Effects of different beta-receptor antagonists on handgrip in essential hypertension.

To assess the influence of selective and nonselective beta blockers with or without ISA we evaluated the extent of pressor responses to isometric exercise in 15 hypertensive patients who had first been treated with atenolol (100 mg/day) and subsequently with mepindolol (15 mg/day) for 2 months each following placebo administration for 2 weeks. Isometric handgrip was always performed in a supine position. Blood pressure and heart rate were measured at 30% of the maximal voluntary contraction. The percentages of blood pressure increases associated with the isometric test were similar during treatment with the two beta blockers; only heart rate was significantly lower. Systolic and diastolic blood pressures showed a lower increase with mepindolol than with atenolol, but the differences were not statistically significant. In conclusion, cardioselective beta blockers without ISA and nonselective beta blockers with ISA influence systolic and diastolic blood pressure responses to a handgrip of 30% in the same way. Only heart rate shows a lower but rather small increase during the cardioselective drug treatment.

Adrenergic beta-Antagonists↗
PubMed1981

Decreased beta-adrenoceptors in polymorphonucleates in essential hypertension.

Number and affinity of beta-adrenoceptors in human polymorphonucleates (PMN's) have been studied in patients with essential hypertension (n = 12) and in normal subjects of the same range of age and sex (n = 16). (-)Diidroalprenolol-H3 has been utilized as ligand. Membranes preparation was performed according to Galant (5). Number of beta-adrenoceptor is significantly decreased compared with controls (p less than 0.05), both with saturation curves and Scatchard analysis. Affinity of beta-adrenoceptors toward (-)diidroalprenolol-H3 is lightly increased but not significantly. These data could be explained on the basis of the desensitization occurring in hypertensive subjects by altered plasma catecholamines level, as in experimental in vitro systems.

Adult↗
PubMed1981

[Instrumentation and methods in policardiography (author's transl)].

Although policardiography has been in use for more than a century, only recently attention has been focused on instrumental and methodological problems of the technique. Among these, frequency response and time constant of the equipment are in first place. Time constant must be long enough to allow an accurate recording of the low and ultra-low frequency vibrations which are generated in the cardio-aorto-hemic system, in particular of those constituting the carotid pulse and the apexcardiogram. The authors stress the influence that incidental air leaks in the recording assembly, or type and size of the pickup device, have on the value of the time constant. Kinetocardiography seems preferable to apexcardiography in order to reproduce with higher fidelity absolute movements of the anterior thoracic wall in every single point.

Carotid Arteries↗