Biomedical subjects

C Troffa

Publications and source records attributed to C Troffa.

At least 37 records · Page 2Linked to original sources

PubMed1990

Effect of a kinin antagonist on renal function and haemodynamics during alterations in sodium balance in conscious normotensive rats.

1. To evaluate whether sodium intake can modulate the action of endogenous kinins on renal function and haemodynamics, a receptor antagonist of bradykinin was infused in conscious normotensive rats maintained on either a normal or a low sodium diet. 2. The antagonist inhibited the hypotensive effect of exogenously administered bradykinin. It did not change the vasodepressor effect of acetylcholine, dopamine or prostaglandin E2. 3. The antagonist did not affect mean blood pressure, glomerular filtration rate, renal blood flow or urinary sodium excretion, in rats on sodium restriction. It did not change mean blood pressure, glomerular filtration rate or urinary sodium excretion, but decreased renal blood flow, in rats on a normal sodium intake. 4. The kallikrein-kinin system has a role in the regulation of renal blood flow in rats on a normal sodium diet.

Animals↗

PubMed1990

Efficacy of nifedipine to prevent systemic and renal vasoconstrictor effects of endothelin.

We investigated whether systemic and renal vasoconstriction induced by porcine endothelin (endothelin 1) is prevented by nifedipine in awake normotensive rats. Endothelin (0.07-1.4 nmol/kg iv) induced a long-lasting increase in mean blood pressure (MBP) and a decrease in renal blood flow (RBF). Maximal decrease in RBF was 25 +/- 7% (0.07 nmol/kg), 40 +/- 2 (0.35), 67 +/- 5 (0.70), and 74 +/- 8 (1.4). Hemodynamic parameters were back to base line within 35 +/- 5 min (0.07 nmol/kg), 43 +/- 6 (0.35), 60 +/- 4 (0.70), and 81 +/- 7 (1.4). Intravenous bolus injection of either angiotensin II (ANG II, 0.006-0.024 nmol/kg) or norepinephrine (0.40-1.60 nmol/kg) caused a dose-related short-lasting increase in MBP and a decrease in RBF. Endothelin was less potent than ANG II (1:3.42) and more potent than norepinephrine (1:0.015) as a renal vasoconstrictor. Nifedipine (1 mg/kg ip) was equally effective in preventing the increase in MBP caused by endothelin, norepinephrine, or ANG II. It exerted a weaker protection on the renal hemodynamic response to endothelin compared with the inhibition of the other two vasoconstrictors. Thus the regression line representing the relationship between endothelin-induced changes in MBP and RBF was steeper in rats given nifedipine (slope: vehicle, -1.33; nifedipine, -5.50; P less than 0.05). These studies suggest that nifedipine can partially prevent systemic and renal vasoconstriction caused by exogenously administered endothelin in awake normotensive rats.

Angiotensin II↗

PubMed1990

Changes in plasma atrial natriuretic factor during sequential fluid removal and biochemical correction in end-stage chronic renal failure patients.

Plasma immunoreactive atrial natriuretic factor (ANF) levels, their chromatographic profiles (high-performance liquid chromatography; HPLC) and changes during sequential ultrafiltration (UF; 1 litre/h) and biochemical correction without fluid removal (BC; 3 h) were studied in 8 end-stage chronic renal failure patients on intermittent haemodialysis (greater than 1 year). Patients entered randomly the UF-BC or BC-UF protocols that were reversed after 1 week. HPLC showed a single peak of ANF immunoreactivity in plasma of end-stage chronic renal failure patients before dialysis sessions. ANF at the end of fluid removal fell by 31 +/- 2% (p less than 0.01) during UF-BC and by 30 +/- 2% (p less than 0.01) at the end of BC during BC-UF. In both sequences a further slight reduction in plasma ANF was observed during the second phase: it was 8.5 +/- 5% (n.s.) during BC of the BC-UF and 12.5 +/- 2% (p less than 0.05) during fluid removal of BC-UF. Plasma ANF was not significantly removed by the machinery. BC did not modify the microhaematocrit in the BC-UF sequence while the microhaematocrit was significantly increased by UF (13 +/- 1 and 14 +/- 1%, p less than 0.005 vs. basal, respectively), and decreased by BC in the UF-BC sequence (-5 +/- 2% vs. end UF, p less than 0.05). Serum creatinine and urea decreased significantly during BC in both protocols while they were unmodified during UF. No significant changes were seen in PRC during either protocol.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗

PubMed1990

Brain kinins are responsible for the pressor effect of intracerebroventricular captopril in spontaneously hypertensive rats.

The role of the brain kallikrein-kinin system in the regulation of arterial blood pressure of normotensive and spontaneously hypertensive rats was evaluated. Intracerebroventricular administration of the kinin antagonist [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin caused no change in mean blood pressure in Wistar-Kyoto, Sprague-Dawley, or spontaneously hypertensive rats. The antagonist proved to be very potent in blocking the pressor effect of intracerebroventricular bradykinin (32 +/- 3 vs. 3 +/- 1 mm Hg, p less than 0.01). It was specific, as the pressor effect induced by other unrelated peptides was similar during the infusion of either vehicle or kinin antagonist (angiotensin II, 25 +/- 4 vs. 26 +/- 2 mm Hg; prostaglandin E2, 48 +/- 3 vs. 47 +/- 8 mm Hg; norepinephrine, 17 +/- 2 vs. 18 +/- 2 mm Hg; leucine-enkephaline, 15 +/- 2 vs. 16 +/- 1 mm Hg; neurotensin, 18 +/- 2 vs. 19 +/- 1 mm Hg; substance P, 19 +/- 2 vs. 19 +/- 2 mm Hg). Intracerebroventricular administration of 1 mg captopril, an inhibitor of kininase II (one of the enzymes responsible for kinin degradation), caused no change in mean blood pressure in normotensive rats, whereas it increased mean blood pressure by 44 +/- 9 mm Hg (p less than 0.01) in spontaneously hypertensive rats. This increase in mean blood pressure was blocked and then reversed into a hypotensive effect (22 +/- 6 mm Hg, p less than 0.05) during the infusion of kinin antagonist. Our data suggest that the pressor effect induced by intracerebroventricular captopril is due to a transient elevation in endogenous brain kinin levels, supporting the hypothesis that the brain kallikrein-kinin system plays a role in the central regulation of blood pressure in spontaneously hypertensive rats.

Animals↗

PubMed1990

[Effect of menstrual cycle hormones on cation transport in the red-cell membrane].

Erythrocyte cation transport, plasma prorenin and renin and sexual hormones were sequentially evaluated in 12 normal volunteers over the menstrual cycle. Na-K cotransport and Na-Li countertransport raised in 6 out of 12 subjects in synchronization with the ovulatory phase. When the maximal % variation (ovulatory phase) versus baseline (follicular phase) of the Na-K cotransport was plotted versus the maximal % increment of oestrogens. A direct, highly significant inverse correlation was observed (r = 0.904, p less than 0.001). Moreover, a highly significant inverse correlation between plasma prorenin and intraerythrocyte Na (r = -0.857, p less than 0.001) in the follicular phase was found. Our data suggest that erythrocyte cation transport can be influenced by sexual hormones in human.

Adult↗

PubMed1990

[Effect of chronic enalapril treatment on prorenin, renin and sex hormones during the menstrual cycle in patients with essential hypertension].

Since angiotensin II seems to be involved in the process of ovulation we studied the effect of chronic enalapril on plasma prorenin, renin, estradiol, progesterone, LH and FSH during the menstrual cycle in ten essential hypertensive women. Our data show that peripheral blockade of A I conversion does not affect the pituitary guidance and the ovarian hormonal response of the menstrual cycle and, we can speculate, that it does not interfere with the process of ovulation.

Adult↗

PubMed1990

[Protective effect of a calcium antagonist against renal vasoconstriction induced by endothelin in the normotensive rat].

We studied the effect of nifedipine, a dihydropyridine calcium antagonist, on the hemodynamic changes induced by endothelin, in awake normotensive rats. Endothelin (0.07-1.40 nmol/kg, e.v.) caused an initial hypotensive effect, followed by long lasting hypertension. Renal blood flow was reduced immediately and still remained below basal levels, at 30 minutes after endothelin injection. Nifedipine (1 mg/kg, i.p.) significantly prevented the effect of endothelin on mean blood pressure and induced a right-ward shift in the dose response curve of renal hemodynamic changes induced by endothelin. We conclude that treatment with calcium antagonist could be very useful in all those conditions in which systemic and regional vasocostriction is provoked by endothelin.

Animals↗

PubMed1989

Circulating prorenin and renin in response to intravenous adrenocorticotrophic hormone in essential hypertension.

Plasma prorenin and renin changes after a bolus injection of 25 U intravenous adrenocorticotrophic hormone (ACTH, synacthen) were studied in seven untreated uncomplicated essential hypertensives over a period of 24 h. Plasma prorenin did not change significantly during the study, whereas renin after 24 h was higher than at baseline (4.3 +/- 0.6 versus 2.3 +/- 0.9 ng angiotensin I (Ang I)/ml per h, P less than 0.01). We conclude that endogenous glucocorticoid stimulation induced by exogenous ACTH and ACTH itself seem to induce a secondary or tertiary rather than a primary effect on the human renin gene.

Adrenocorticotropic Hormone↗

PubMed1989

Correlates of atrial natriuretic factor in chronic renal failure.

Plasma atrial natriuretic factor (ANF), blood pressure, age, plasma renin activity and creatinine were measured in 50 normal volunteers, 141 essential hypertensives, 35 patients with chronic renal failure who had never been dialysed and 27 patients with end-stage renal failure on constant haemodialysis. Plasma ANF was correlated positively with age in the normal group (r = 0.52, P less than 0.01) and with blood pressure in the essential hypertensives (r = 0.50, P less than 0.001), and negatively with renin in the normal and end-stage renal failure patients (r = -0.47, r = -0.34; P less than 0.01, P less than 0.05, respectively). When patients without left ventricular hypertrophy were matched for age and blood pressure, plasma ANF was significantly different between the essential hypertensives and the normal and end-stage renal failure patients (16 +/- 1, 38 +/- 6 and 148 +/- 24 pmol/l, respectively; P less than 0.001). Cardiac factors are therefore not the only determinant of circulating plasma ANF in humans with chronic renal failure.

Aging↗

PubMed1989

Effect of endothelin on regional hemodynamics and renal function in awake normotensive rats.

The effects of endothelin on regional hemodynamics and renal function were studied in awake normotensive rats. Intravenous injection of endothelin (700 pmol/kg) transiently lowered mean blood pressure (from 108 +/- 2 to 84 +/- 2 mm Hg, p less than 0.01), due to a reduction in total vascular resistance (38 +/- 1%, p less than 0.01), and increased stroke volume (29 +/- 5%, p less than 0.01) and heart rate (from 399 +/- 18 to 447 +/- 18 bpm, p less than 0.05); mesenteric and renal blood flow was reduced (37 +/- 13, p less than 0.05 and 63 +/- 5%, p less than 0.01), whereas carotid blood flow was increased (78 +/- 5%, p less than 0.01). This effect was followed by long-lasting hypertension due to increased total vascular resistance (112 +/- 19%, p less than 0.01); stroke volume, mesenteric, and renal blood flow were reduced (34 +/- 5, 41 +/- 4, and 58 +/- 4%, respectively, p less than 0.05) and carotid blood flow returned to basal levels. Bilateral nephrectomy enhanced the initial hypotensive effect. Pretreatment with nifedipine blocked the hypertensive effect, whereas bilateral nephrectomy did not. A subpressor dose of endothelin (70 pmol/kg) had no effect on stroke volume, mesenteric blood flow, glomerular filtration rate, and plasma renin activity; carotid blood flow was transiently increased (48 +/- 16%, p less than 0.05), then returned to basal levels; renal blood flow decreased (22 +/- 6 and 15 +/- 4% at 30 s and 10 min, respectively p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1989

Stimulation of plasma inactive renin by dexamethasone in the cat.

An inactive form of renin in human plasma is the biosynthetic precursor, prorenin. The cat is a good animal model for studies of inactive renin. The gene for human renin contains sequences homologous to the glucocorticoid consensus sequence. The response of cat plasma (active and inactive renin) and of angiotensinogen to administration of dexamethasone (0.5 mg/kg im, daily) was studied in ketamine-sedated cats (20 mg/kg im). Inactive renin increased by twofold after 7 days of dexamethasone (P less than 0.01). After a 7-day recovery period, it returned to base line. Active renin did not change. Angiotensinogen fell by 35% (P less than 0.01). The time course of the selective increase of plasma inactive renin showed that inactive renin began to rise after 2 days, peaking after 5 days. Ketamine alone induced inactive renin to rise slightly but significantly (P less than 0.05), although the magnitude of the increment was much less than that observed in ketamine-sedated cats receiving dexamethasone (P less than 0.01). Active renin did not change, whereas angiotensinogen was reduced by 25% (P less than 0.01). Our findings support the hypothesis that glucocorticoids might have a selective role in the synthesis and/or secretion of the precursor of renin, at least in the cat.

Angiotensinogen↗

PubMed1989

Low-dose infusion of atrial natriuretic factor in mild essential hypertension.

Intra-arterial blood pressure, cardiac output, heart rate, right heart indexes, urinary electrolytes, and urinary volume were monitored in eight patients with untreated (WHO Class I) essential hypertension. The patients were given synthetic atrial natriuretic factor (ANF) (99-126 alpha-hANP) at 1 and 2 pmol/kg/min in series (phases 1 and 2, 2 hours each dose) or vehicle (hemaccel) in random order on two separate occasions while on their usual diet. Arterial plasma ANF levels increased significantly from basal and time-matched placebo values from 25 +/- 2 and 28 +/- 3 pmol/l to 50 +/- 4 and 83 +/- 9 pmol/l at the end of phases 1 and 2, respectively (p less than 0.001). After 30 minutes during phase 2, systolic blood pressure decreased significantly by 20 +/- 4 mm Hg (p less than 0.001) from basal and time-matched placebo values and remained significantly reduced (-17 +/- 4 mm Hg, p less than 0.001) by the end of the recovery period (2 hours after infusions were completed). Pulmonary systolic blood pressure decreased by 5 +/- 1 mm Hg (phase 2, p less than 0.05). Cardiac output decreased by 0.5 +/- 0.1 l/min below baseline at the end of phase 2 of ANF infusion, whereas it increased significantly (p less than 0.02) by 0.6 +/- 0.1 l/min during vehicle infusion. Systemic diastolic, pulmonary diastolic, right atrial, and wedge pressures were not significantly changed during ANF or vehicle infusions, nor were pulmonary vascular resistance or heart rate altered. Systemic vascular resistance did not change significantly during both infusions, whereas during recovery, systemic vascular resistance decreased significantly after ANF infusion was discontinued (p less than 0.05). Microhematocrit levels increased dose dependently during ANF. The maximum increase was observed at the end of phase 2 (+4.7 +/- 1.7%), whereas the microhematocrit level decreased to -2.4 +/- 0.6% with vehicle (p less than 0.001) at the end of phase 2. Urinary sodium excretion increased significantly (p less than 0.02) by the end of phase 2 under ANF infusion (+38 +/- 15%), whereas it decreased (-10 +/- 6%) under placebo infusion by the end of phase 2. Urinary magnesium excretion was significantly increased during ANF infusion from phase 1 (p less than 0.02), whereas urinary potassium levels, calcium levels, creatinine levels, volume, and glomerular filtration rate did not differ significantly between the two infusions. Plasma renin, angiotensin II, aldosterone, and catecholamine concentrations did not change significantly during ANF or vehicle infusions.(ABSTRACT TRUNCATED AT 400 WORDS)

Atrial Natriuretic Factor↗

PubMed1989

[Erythrocyte cation transport in arterial hypertension: interrelation with the renin-angiotensin-aldosterone system and the atrial natriuretic factor].

Red cell membrane Na(+)-K+ transport systems, renin-angiotensin-aldosterone system (RAAS) and atrial natriuretic factor (ANF) were studied in a group of 50 mild essential hypertensive patients (n = 25 for each group) age, sex and blood pressure matched. Na(+)-K+ ATPase and intracellular Na+ (Na+ i) were significantly different between the two groups (p less than 0.01). A slight difference was also seen for the Na(+)-K+ cotransport (p less than 0.05) as a likely consequence of the differences in the methodology of Na+ charge to study its efflux from the red cells in vitro. A negative correlation (r = -0.47, p less than 0.01) was observed between ANF and Na(+)-K+ cotransport suggesting an interrelationship of the two systems in the homeostasis in body fluid and electrolytes.

Adult↗

PubMed1989

Activation of human prorenin by lipidic constituents of the cell membrane.

Activation of semipurified human kidney prorenin was found to occur in vitro in presence of a mixture of lipids that mimics the composition of the inner human cell membrane. The lipid-dependent activation was indeed only partial (38 +/- 4%) when compared to that obtained by trypsin in liquid phase (100 micrograms/mL) used as a control of maximal activation (100%) under our experimental conditions (semipurified human kidney prorenin in presence of semipurified human plasma renin substrate at a concentration of 1400 ng/mL, at pH 7.2). The phenomenon was time-dependent up to 60 min whereas the angiotensin I generated after 120 min was virtually the same as that generated after 60 min thus indicating a possible reversible activation of human prorenin. We speculate that prorenin may be reversibly activated by contact with the lipidic portion of the cell membrane either inside or outside the cells thus allowing a limited angiotensin II-generating cascade at a local site initiated by prorenin independently from the presence of active renin.

Angiotensin I↗

PubMed1989

[Possible activation of human prorenin by contact with the cell membrane].

Semipurified human kidney prorenin was exposed in vitro to a mixture of lipids mimicking the composition of the inner leaflet of the cell membrane, in the presence of semipurified human angiotensinogen at a concentration of 1/4 Km. Prorenin was activated in a time-dependent manner over a period of 60 min. This lipid-dependent activation was completely reversed thereafter. Pre-incubation with anti-renin serum completely prevented this activated prorenin-dependent generation of angiotensin I. Our data suggest that human prorenin can be reversibly activated by contact with the cell membrane.

Angiotensin I↗

PubMed1988

Prorenin in the cells of the mature human ovarian follicle.

Angiotensin I generating capacity in presence of semi-purified plasma human angiotensinogen, before and after liquid phase trypsin activation, was found in the extracts of the cells retrieved from human hyperstimulated ovarian follicles in women undergoing in-vitro fertilization. More than 90% of this AI generating capacity was due to activated prorenin, whereas only less than 10% was due to active renin. Low levels of angiotensinogen were also present in the extracts (100 ng/ml). This AI forming capacity was completely abolished by pre-incubation with polyclonal anti-renin serum. More than 90% of the cells retrieved from the ovarian follicles were granulosa cells. An intracellular prorenin-renin system can exist in the human ovary than can modulate the ovarian function throughout the menstrual cycle and during pregnancy.

Adult↗

PubMed1988

Effects of nitrendipine on blood pressure, renin-angiotensin system, and kidney function in essential hypertension.

The effects of nitrendipine (10 mg b.i.d.) on blood pressure, renin-angiotensin-aldosterone system, and kidney function (by means of glomerular and tubular function) were studied in comparison to captopril (50 mg b.i.d.) and to nitrendipine (10 mg q.d.) + captopril (25 mg b.i.d.) in 30 untreated essential mild-to-moderate hypertensives. The blood pressure lowering effect was similar with either regimen. Nitrendipine showed an acute and chronic natriuretic effect not accompanied by modifications of kidney function. All regimens were well tolerated by the patients without any appreciable side effects over the 4-week study period.

Adult↗

PubMed1987

Natriuretic effect of acute nifedipine administration is not mediated by the renal kallikrein-kinin system.

Despite their vasodilating action, calcium antagonists increase renal sodium excretion. To ascertain whether renal kallikrein plays a role in the renal effects of calcium antagonists, nifedipine (N) (10 mg orally) or placebo (P) was given to 17 male patients with mild to moderate essential hypertension during a 6-h infusion of either saline (S) or aprotinin (A) (2 X 10(6) KIU in 200 ml of saline). Blood pressure (BP) and heart rate (HR) were measured every 10 min, and blood samples were taken at -10, 0, 30, 60, 120, 240, 360 min for plasma renin activity (PRA), creatinine, and osmolarity determinations. Urinary kallikrein, aldosterone, creatinine, and electrolytes were measured in 6-h urine collections. The acute administration of N induced a significant systolic BP (SBP) and diastolic (DBP) fall and a transient PRA increase that peaked at 30 min and were not modified by A infusion. Urinary volume (+47%), Na+ (+54%) and Cl- (+58%) excretion were significantly enhanced by N. There were less pronounced and statistically not significant increases in urinary excretion of Ca2+ (+38%) and K+ (+29%). Infusion of A did not interfere with the natriuretic effect of N. Our data do not support the hypothesis that the kallikrein-kinin system plays an important role in mediating the renal effects of nifedipine in humans.

Adult↗