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Biomedical subjects

P Salvati

Publications and source records attributed to P Salvati.

52 records · Page 3Linked to original sources
PubMed1988

Renal abnormalities at the prehypertensive stage of essential hypertension.

An approach to evaluating the genetic components of essential hypertension using an animal model, the Milan hypertensive strain (MHS) of rats, and studies in human families with positive and negative histories for high blood pressure are described and discussed. Differences at renal and cellular levels between MHS and its normotensive control strain, MNS, show many similarities to those between offspring from hyper- and normotensive families in humans. These include, with respect to the former group of each species, lower erythrocyte volume and Na content, higher Na-K cotransport across red blood cell (RBC) membranes higher Na excretion after load, and greater pressor effect in transplanted kidneys. A novel protein found in rat RBC cytoskeleton appears to have a function in Na-K cotransport and it may, eventually, be possible to demonstrate in man.

Animals↗
PubMed1987

Renal function of isolated perfused kidneys from hypertensive (MHS) and normotensive (MNS) rats of the Milan strain: role of calcium.

Abnormal sodium (Na+) and water handling by the kidney may be the cause of hypertension in rats of the Milan hypertensive strain (MHS). In addition, the plasma cell membrane Ca-ATPase at Vmax is lower in MHS than in normotensive controls (MNS). The isolated kidney preparation was used to explore the role of extracellular free calcium (Ca2+) concentrations (1.25, 1.00 and 0.75 mmol/l) in tubular Na+ transport of pre-hypertensive MHS rats. At the Ca2+ concentration of 1.0 mmol/l, the following parameters were significantly higher (P less than 0.01) in MHS: glomerular filtration rate (GFR) and urinary volume (UV), +104.8 and +147.2%, respectively; urinary Na+ excretion (UNa+), +318.0%; tubular Na+ reabsorption (TNa+), +91.0% and oxygen consumption Q O2, +42.9%. Raising the Ca2+ concentration to 1.25 mmol/l increased UV (+167.0%) and UNa+ (+231.0%) in MHS without substantially affecting MNS. The difference between the two strains was therefore considerably larger for these parameters, but disappeared for TNa+ and Q O2. The overall kidney function of MHS was poor as compared wit renal function at Ca2+ 1.0 mmol/l. The differences between the two strains virtually disappeared at the lowest Ca2+ concentration (0.75 mmol/l); only GFR and TNa+ remained slightly greater in MHS mainly because of the poor viability of MNS kidneys in this experimental condition. It thus appears that the lower activity of Ca2+-ATPase of MHS compared with MNS plasma cell membranes influences the differences in Na+ and water handling in the two strains.

Animals↗
PubMed1987

Antihypertensive ergoline derivatives.

Novel ergolines were synthesized and screened in spontaneous hypertensive rats (SHR) with the aim of finding a new class of ergot related antihypertensives. Their prolactin inhibitory effect (measured as nidation inhibition in rats), acute toxicity (LD50) and interference with CNS function (Irwin test) were also evaluated as a measure of selectivity and safety. Modification of the C8 side-chain enhanced antihypertensive activity selectively, while the introduction of substituents in other positions of the ergoline skeleton generally yielded unfavourable results, either by decreasing selectivity or by increasing toxicity.

Animals↗
PubMed1986

Renal mechanisms and calcium in the pathogenesis of a type of genetic hypertension.

Results concerning kidney and red blood cell (RBC) function of Milan hypertensive rats (MHS), and of their age- and body weight-matched normotensive controls (MNS), are summarized. Our data suggest a biochemical and physiological link between RBC abnormalities and the renal mechanisms causing hypertension in MHS, and therefore the possibility of using the former as a tool for studying the genetic biochemical mechanisms of hypertension. In particular, the following results are discussed: a positive correlation between blood pressure and RBC Na+-K+ cotransport found in the F2 generation, obtained by crossing F1 (MHS X MNS) hybrids; bone marrow transplantation from MHS and MNS into F1 hybrids, causing a parallel change in recipient RBC characteristics; and similarities between erythrocytes and renal tubular cells in Na+ content, cell volume, and Na+ transport. Ca2+ ATPase or Ca2+ pump at Vmax are lower in MHS renal tubular cells and MHS erythrocytes than in MNS cells. Moreover, isolated kidneys of MHS and MNS, perfused in vitro with media at different Ca2+ concentrations, showed that the function of MNS kidney remained stable over a range of Ca2+ from 0.75 to 1.25 mM, while the function of MS kidney deteriorated at a Ca2+ concentration of 1.25 mM.

Adult↗
PubMed1986

A renal abnormality in the Milan hypertensive strain of rats and in humans predisposed to essential hypertension.

Many similarities in kidney-function abnormalities were found between hypertensive rats of the Milan strain (MHS) and young normotensive human subjects with hypertensive parents, compared with the appropriate controls. These similarities included an increased glomerular filtration rate, increased pressor effect of the kidney after transplantation, increased 24-h urinary output and lower plasma renin activity and urinary kallikrein. The isolated MHS kidney perfused in vitro with an artificial medium had a higher glomerular filtration rate, a higher urinary output, higher tubular sodium reabsorption and higher oxygen consumption than the kidney of control Milan normotensive rats (MNS). Further, reogenic sodium transport across brush border vesicles isolated from proximal tubular cells is faster in MHS than in MNS. Erythrocytes and proximal tubular cells of MHS have a lower volume and sodium content than those of MNS, while sodium transport is faster and the Ca2+-ATPase at Vmax is lower. This indicates that the 'genetic' cellular abnormality responsible for the renal-function abnormality and the hypertension is also present in erythrocytes. Thus these cells may be used to study the genetic cellular mechanisms of hypertension. Experiments with bone marrow transplantation and with F2 hybrids obtained by crossing the F1 (MHS X MNS) hybrids showed that the MHS erythrocyte abnormalities are genetically determined within the stem cells and are genetically associated with the hypertension. Since, in human hypertensives, there was a correlation between abnormal erythrocyte sodium transport and renal function, it is proposed that erythrocytes may be used in studying the cellular molecular mechanisms of hypertension.

Animals↗
PubMed1985

Presence of a potential-sensitive Na+ transport across renal brush-border membrane vesicles from rats of the Milan hypertensive strain.

Sodium transport was measured in brush-border membrane vesicles prepared from kidney cortex of the Milan hypertensive strain (MHS) rats and the corresponding normotensive controls. In the presence of an outwardly directed proton gradient, 22Na was transiently accumulated in the vesicles. When a transmembrane electrical potential was imposed across membrane vesicles, both the accumulation ratio and the initial uptake were increased, indicating the presence of an electrogenic pathway for sodium in these membranes. The potential-dependent sodium uptake was significantly higher in MHS rats. Kinetic analysis give simple Michaelis Menten curves in the presence and in the absence of a membrane potential. In both conditions Jmax was significantly increased in MHS rats, whereas Km was the same for the two rat strains. Sodium uptake was inhibited by amiloride at concentrations that inhibit Na+-H+ exchange. The presence of the higher, potential-sensitive, sodium uptake in MHS is in agreement with studies on renal physiology which support the hypothesis that an increase in tubular sodium reabsorption may be the primary cause for the development of hypertension in this rat strain.

Amiloride↗
PubMed1985

Involvement of peripheral dopamine receptors in the antihypertensive effect of a new ergoline derivative (355/1057).

Oral administration of a new ergoline derivative (355/1057) produced a sustained arterial hypotension in conscious SHR rats. This effect was inhibited by the centrally acting DA blockers haloperidol and pimozide and by domperidone, a DA antagonist that does not cross the blood brain barrier. On the other hand it was unaffected by alpha- and beta-adrenoceptor blockers or by indomethacin. Moreover, the hypertension induced by 355/1057 in pithed SHR rats was reversed to hypotension when its alpha-adrenoceptor stimulant activity was inhibited by yohimbine. In anesthetized dogs the hypotensive activity of 355/1057 was abolished by pimozide but not by propranolol. In anesthetized cats, pretreatment with haloperidol prevented both the hypotensive activity of 355/1057 and its inhibitory effect on sympathetic nerve activity. These overall data suggest that 355/1057 lowers blood pressure in different species mainly by stimulating peripheral dopamine receptors.

Anesthesia↗
PubMed1984

Renal function of isolated perfused kidneys from hypertensive (MHS) and normotensive (MNS) rats of the Milan strain at different ages.

Young pre-hypertensive rats of the Milan strain (MHS) have a faster glomerular filtration rate (GFR) and a higher urine flow in vivo than matched normotensive controls (MNS). Kidneys from both MHS and MNS at different ages were perfused in vitro with cell-free artificial medium, in order to further clarify the nature of these differences, in the absence of extrarenal uncontrolled factors. Isolated kidneys from young MHS showed a faster GFR, a larger tubular Na+ reabsorption and urine flow as compared to matched MNS: such differences endured throughout the 2 h of perfusion. These results support an intrinsic kidney abnormality as causing the above described differences between young rats of the two strains. Isolated kidneys from adult MHS showed faster GFR, higher renal perfusion flow and urine flow, yet similar tubular Na+ reabsorption when compared to MNS. Moreover a faster decay in kidney function was observed in the experiments with MHS. The existence of an extrarenal factor(s) correcting the intrinsic MHS kidney abnormality in vivo is suggested, as no differences were reported in kidney function of intact adult animals.

Absorption↗
PubMed1983

Vascular responses of the isolated perfused stomach of rabbit and rat to histamine.

Gastric vascular responses to histamine and its selective H1- and H2-agonists in vitro were investigated in the isolated vascular-perfused stomach of rabbit and rat. In the rabbit stomach under resting conditions bolus injection of histamine (5-80 nmol) caused a small increase in perfusion pressure (PP). However, during infusion of noradrenaline (1 microM), which elevated vascular tone, histamine (5-80 nmol) caused a dose-dependent biphasic vascular response, an initial increase followed by a fall in PP. Under similar conditions, the H1-agonist 2-pyridyl ethylamine, (2-PE; 50-400 nmol) elevated PP, whereas the H2-agonist dimaprit (80-640 nmol) reduced PP. The H1-antagonist mepyramine (0.25 microM) converted the biphasic response of histamine (5-50 nmol) to a monophasic vasodilation whereas the H2-receptor antagonist, cimetidine (1 microM) converted the biphasic response to a vasoconstriction. Similar responses were observed during conditions of elevated vascular tone induced by vasopressin or angiotensin II. In the rat stomach, histamine and both dimaprit and 2-PE reduced PP during conditions of elevated vascular tone. These findings support the presence of both H1- and H2 receptors in the gastric vasculature of both rat and rabbit; in both species, the H2-response is vasodilation whereas the nature of the H1-response is species dependent.

Animals↗
PubMed1983

Antihypertensive ergolinepropionamides.

The synthesis and the antihypertensive activity in rats of a series of 6-methylergolin-8 beta-yl-propionic acid derivatives are reported. The prolactin lowering activity (nidation inhibition test) in rats and the acute toxicity in mice were also studied as a measure of the specificity and safety of the potential antihypertensive compounds. From the structure-activity considerations reported here it is clear how modifications at the C8 side chain can improve the selectivity of the antihypertensive effects, whilst introducing substituents in other positions of the ergoline skeleton afforded unfavourable results in this respect. Compound 5, namely 2(R,S)-cyano-3-(6-methylergolin-8 beta-yl)-propionamide, emerged as the most interesting antihypertensive derivative.

Animals↗
PubMed1983

Cardiovascular effects of a new antihypertensive agent in several species.

The effects on blood pressure and heart rate of a new ergoline derivative, 2(R,S)-Cyano-3-(6-methylergolin-8 beta-yl)-propionamide (355/1057), were evaluated in different models of experimental hypertension as well as in normotensive rats, dogs and cats. Its interference with sympathetic neurotransmission was also studied in anaesthetized cats and dogs and in pithed rats. Dose-related hypotensive effects were found after single oral, intraduodenal and intravenous administration. In all the studied experimental models 355/1057 showed a prompt onset of action and a prolonged effect on blood pressure at low doses without substantially modifying heart rate. Some comparative results obtained with other commercially available antihypertensive agents are also reported. One month daily oral administration in SH-rats produced an antihypertensive effect persisting trough the entire experiment with no signs of tachyphylaxis. In anaesthetized dogs 355/1057 inhibited sthe pressor response elicited by bilateral carotid occlusion and in anaesthetized cats it reduced the response of the nictitating membrane elicited by electrical stimulation of both the pre- and post-ganglionic fibers but not by norepinephrine bolus injection.

Anesthesia↗
PubMed1981

Investigation of the vascular actions of arachidonate lipoxygenase and cyclo-oxygenase products on the isolated perfused stomach of rat and rabbit.

The vascular actions of several prostanoids and arachidonate lipoxygenase products were investigated on the gastric circulation of rat and rabbit in vitro perfused with Krebs' solution. Under resting conditions, prostacyclin and PGE2 produced small decreases in perfusion pressure with prostacyclin being the more potent. During vasoconstriction induced by infusion of noradrenaline, vasopressin or angiotensin II, prostacyclin was 20-40 times as active as PGE2 as a gastric vasodilator in rat or rabbit stomach. PGF2 alpha was a less potent vasoconstrictor than noradrenaline, while the epoxy-methano endoperoxide analogue produced a long-lasting vasoconstriction. The putative metabolite, 6-oxo-PGE1 was less active than prostacyclin as a vasodilator, having comparable activity to PGE1, whereas 6-oxo-PGF1 alpha had very little activity. The endoperoxide, PGH2 reduced perfusion pressure, this effect being inhibited by concurrent infusion of 15-HPETE. The vasodilation induced by arachidonic acid was likewise reduced by 15-HPETE, and abolished by indomethacin infusion. The arachidonate lipoxygenase hydroperoxides were vasodilator in the gastric circulation, the rank order of potency being 12-HPETE greater than 11-HPETE greater than 5-HPETE greater than 15-HPETE in both rat and rabbit stomach. It is possible that such vasoactive lipoxygenase products, may play modulator roles in the gastric mucosa.

Animals↗