Biomedical subjects

N Glorioso

Publications and source records attributed to N Glorioso.

At least 73 records · Page 4Linked to original sources

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↗

PubMed1988

The ovarian prorenin-angiotensin system. Lessons from IVF.

Recent evidence suggests that prorenin and other active components of the renin-angiotensin system may be linked to ovarian physiology. Prorenin, the inactive form of the enzymatically active renin, is present in the fluid of mature human ovarian follicles in concentrations more than 10 times higher than that found in the plasma of women undergoing ovarian stimulation. Only 1% of the renin in follicular fluid is in active form. Concentrations of prorenin in fluid of immature follicles are lower than levels detected in concomitantly aspirated mature follicles. Study of prorenin levels disclosed a positive correlation to testosterone and E2 in fluids of mature follicles. Plasma prorenin increases about twofold at midcycle at the time of the LH surge; the peak of prorenin is sustained for about 40 hours. In patients undergoing ovarian stimulation for IVF, hCG administration results in much higher plasma prorenin levels and the height of prorenin response is directly related to the number of mature follicles. It peaked 4 to 6 days after hCG injection and then fell, close to baseline, by about 12 days after hCG administration. Examination of the time course of hormonal changes in response to hCG revealed a temporal relationship between prorenin and both plasma E2 and progesterone. In women who conceived, prorenin began to rise again on days 8 to 12 after embryo transfer when endogenous hCG was detected in the blood. No such changes in prorenin occurred in women with ovarian failure who conceived after transfer of a donor egg. These findings indicate that prorenin is produced by the mature follicle and the corpus luteum in response to LH/hCG. Since angiotensin II affects intracellular calcium and phospholipase activity, there are many potential roles for prorenin via angiotensin II action. Putative actions of the ovarian renin system may include control of oocyte maturation, ovulation, ovarian blood flow, and ovarian steroid biosynthesis. Future work to elucidate the function of this new renin system may have relevance to many basic and clinical aspects of human reproduction.

Enzyme Precursors↗

PubMed1988

Plasma clearance and effects of alpha-hANP infused in patients with end-stage renal failure.

The effects and clearance of synthetic atrial natriuretic peptide (alpha-hANP) were investigated in eight patients with end-stage renal failure and six normal volunteers. ANP or vehicle was infused for 1 h at 10 pmol.kg-1.min-1 in random order on two separate occasions. During ANP infusions in end-stage renal patients, microhematocrit rose by 9.8 +/- 2% (P less than 0.005, n = 8), from base-line values of 0.24 +/- 0.02. Serum protein and albumin rose consistently. In contrast, during placebo infusions, no significant changes were seen. Blood pressure, heart rate, plasma renin concentration, serum creatinine, and electrolytes did not change significantly during either study phase. In end-stage renal failure patients, metabolic clearance rate of infused ANP was 1.04 +/- 0.095 l/min and its plasma half-life was 4 min 34 s. In normal volunteers, metabolic clearance rate was 2.6 l/min and its plasma half-life 3 min 30 s. The data suggest that ANP promotes contraction of plasma volume via a mechanism independent of renal function and also indicate that the kidney is not the only organ involved in the ANP metabolism.

Adult↗

PubMed1988

High prevalence of microproteinuria, an early index of renal impairment, in patients with diffuse psoriasis.

Heavy reversible proteinuria induced by antihypertensive treatment with low doses of captopril has recently been reported by our group in psoriatic patients. To ascertain whether an increased permeability of the glomerular basal membrane of psoriatics can lead to an enhanced urinary excretion of albumin independently from the presence or absence of coexisting diabetes or hypertension, the latter parameter was measured in 39 patients affected by diffuse psoriasis. A high prevalence of microalbuminuria was observed in diabetic and hypertensive psoriatics. Moreover, a direct correlation was found between the diastolic blood pressure (BP) values and the urinary excretion of albumin in the entire group of psoriatics, thus suggesting systemic hypertension as one of the factors responsible for proteinuria in these patients. However, more than 50% of normotensive psoriatics showed an enhanced excretion of albumin. Since microalbuminuria has been indicated as a reliable index to predict the development of renal impairment, the finding of an enhanced albumin loss in psoriatics represents a further risk factor in these patients, who are particularly susceptible to experience cardiovascular complications.

Adult↗

PubMed1988

Prorenin secretion from human testis: no evidence for secretion of active renin or angiotensinogen.

To determine if the testis secretes active renin and prorenin, we collected internal spermatic venous blood from 29 young men undergoing varicocelectomy and measured plasma prorenin and active renin together with angiotensinogen and testosterone. Prorenin was higher in internal spermatic venous plasma than in peripheral plasma (+5.3 +/- 1.2 (+/- SE) ng/mL.h [+1.21 ng/(L.s)]; P less than 0.001) as was testosterone [+344 +/- 32 ng/mL [(+1193 nmol/L; P less than 0.001], but there was no significant difference in either active renin (-0.74 +/- 0.45 ng/mL.h [-0.17 ng/(L.s)] or angiotensinogen [+12 +/- 24 ng/mL (+0.01 mumol/L)]. These results demonstrate that the testis secretes prorenin, but not active renin or angiotensinogen, into the general circulation. They support the hypothesis that extrarenal renin systems cannot process prorenin to renin.

Adult↗

PubMed1987

Urinary kallikrein excretion can predict the blood pressure response to a single oral dose of captopril.

The antihypertensive efficacy of ACE inhibitors depends in theory from the blockade of the angiotensin II formation but also from the inhibition of kinin breakdown. To test whether a blunted activity of the kallikrein-kinin system might account for the failure of ACE inhibitors in lowering BP in patients in whom the renin-angiotensin system is not enhanced, thirty-one essential hypertensives with normal or low PRA were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall both in systolic and diastolic blood pressure (BP) was obtained in the subgroup of patients who were classified as "normal kallikrein hypertensives" according to whether their pretreatment urinary kallikrein excretion was within the normal range, while no significant change in BP was observed in "low kallikrein hypertensives". Furthermore the mean percentage fall in mean BP, throughout the 2 hours following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47, p less than 0.05) in the entire group of patients. Our results suggest that a blunted activity of the kallikrein system might be responsible for failure of captopril in lowering BP in patients in whom the renin-angiotensin system is not pathogenetically implicated.

Administration, Oral↗

PubMed1987

Plasma prorenin response to human chorionic gonadotropin in ovarian-hyperstimulated women: correlation with the number of ovarian follicles and steroid hormone concentrations.

Plasma prorenin and active renin were measured before and after human chorionic gonadotropin (hCG) administration in two groups of patients undergoing ovarian stimulation for 4-6 days with follicle-stimulating hormone alone or in combination with luteinizing hormone, for in vitro fertilization. Baseline total plasma renin (prorenin plus active renin; n = 12) averaged 25 +/- 8 ng/ml per hr (mean +/- SD). Total renin did not change during ovarian stimulation but it increased to 46 +/- 16 ng/ml per hr (P less than 0.05) 1 or 2 days later, just before hCG administration. Thirty-six hours after hCG administration, just before laparoscopy and egg retrieval, total renin was 123 +/- 97 ng/ml per hr; a peak of 182 +/- 143 ng/ml per hr occurred 2-6 days later--i.e., during the luteal phase of the menstrual cycle. In eight of the patients who did not conceive, total renin returned to baseline 14 days after hCG administration. In four who conceived, a nadir was reached (57 +/- 13 ng/ml per hr) 8-12 days after hCG administration and then total renin increased again as the plasma beta hCG measurement began to rise. By day 16 it averaged 225 +/- 157 ng/ml per hr. In a second group of five patients active renin and prorenin were measured separately. Active renin comprised less than 20% of the total renin at all times. It was unchanged until day 4 after hCG administration and then increased significantly only when plasma progesterone was high. Thus, the initial response to hCG was entirely due to an increase in prorenin. A highly significant correlation was observed between the number of follicles and the total renin increases on the day of aspiration (r = 0.93, P less than 0.001) and at the peak (r = 0.89, P less than 0.001). After hCG administration, a temporal relationship was observed between the rise in total renin and plasma estradiol and progesterone levels. These results demonstrate that plasma prorenin increases markedly after administration of hCG and that the rise is directly related to the number of ovarian follicles and to plasma estrogen and progesterone levels. The findings suggest that prorenin is produced by the mature ovarian follicle and by the corpus luteum in response to gonadotropin stimulation.

Chorionic Gonadotropin↗

PubMed1987

The effects of aprotinin, a kallikrein inhibitor, on renin release and urinary sodium excretion in mild essential hypertensives.

The effects of aprotinin on renin release and renal function were evaluated in 24 male essential hypertensive patients, on unrestricted (n = 17) and on chronic low as well as on high sodium intake. Aprotinin (1 X 10(6) kallikrein inhibitor units) or saline (200 ml) were infused in all patients for 6 h. Blood samples were taken for plasma renin activity (PRA) and 6-h urine collections were obtained for active and inactive kallikrein, sodium and potassium excretion measurement. In patients on unrestricted sodium diet, aprotinin had no effect on blood pressure (BP), glomerular filtration rate, renal plasma flow, urinary sodium and potassium excretion. However, an inverse relationship was found between pretreatment urinary sodium excretion and the per cent reduction of the latter after aprotinin. A significant reduction in urinary sodium excretion was induced by aprotinin in patients on high sodium intake, whereas no change was observed in the same patients when on a low sodium diet. Aprotinin reduced the urinary excretion of active kallikrein by 81% and the active to total kallikrein ratio from 24 to 6%. Infusion of aprotinin induced a significant decline in active renin but did not modify inactive renin levels in patients on unrestricted sodium diet as well as in patients on low or high sodium intake. Our data suggest that the inhibition of kallikrein and/or other serine proteases by aprotinin can interfere with renal release of active renin and also support the hypothesis that the renal kallikrein system exerts a regulatory control on sodium excretion in salt replete hypertensives.

Adult↗

PubMed1987

Role of renal kallikrein in modulating the antihypertensive effect of a single oral dose of captopril in normal- and low-renin essential hypertensives.

The antihypertensive efficacy of angiotensin converting enzyme (ACE) inhibitors may result from the blockade of angiotensin II formation but also, theoretically, from the inhibition of kinin breakdown. To test whether a blunted activity of the kallikrein-kinin system might account for the failure of ACE inhibitors in lowering blood pressure (BP) in patients in whom the renin-angiotensin system (RAS) is not enhanced, 31 essential hypertensives with normal or low plasma renin activity (PRA) were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall, in both systolic and diastolic BP, was obtained in the subgroup of patients who were classified as 'normal-kallikrein hypertensives' according to whether their pretreatment urinary kallikrein excretion was within the normal range, while no significant change in BP was observed in 'low-kallikrein hypertensives'. Furthermore, the mean percentage fall in mean BP, throughout the 2 h following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47, P less than 0.05) in all the patients. Our results suggest that blunted activity of the kallikrein system might be responsible for failure of captopril to lower BP in some hypertensive patients.

Adult↗

PubMed1987

Studies on the natriuretic effect of nifedipine in hypertensive patients: increase in levels of plasma atrial natriuretic factor without participation of the renal kallikrein-kinin system.

We studied two groups of hypertensive patients in order to ascertain whether the acute natriuretic effect of nifedipine is mediated by humoral factors such as renal kallikrein or atrial natriuretic factor (ANF). First, 17 patients with mild to moderate essential hypertension maintained on a 130-mmol/day diet, received either nifedipine (10 mg orally) or placebo during a 6-h infusion of the kallikrein inhibitor aprotinin (2 x 10(6) KIU) or saline as control. Aprotinin, while significantly reducing urinary kallikrein activity, did not interfere with the acute effects of nifedipine on blood pressure, heart rate, urinary volume, urinary Na+ and creatinine clearance. In another group of eight patients on a constant daily Na+ intake of 130 mmol and in the supine position, placebo or nifedipine (10 mg sublingually) were administered, and blood pressure, heart rate, plasma renin activity, plasma aldosterone and plasma ANF, urinary Na+, urine volume and creatinine clearance, were monitored for 2 h. While placebo did not induce changes in any of the above parameters, nifedipine administration induced a significant decrease in blood pressure and increase in urinary Na+, urine volume and creatinine clearance, and a significant rise in ANF levels, from 19.4 +/- 2.8 pg/ml to a maximum of 23.9 +/- 2.5 and 24.1 +/- 2.2 pg/ml (P less than 0.05) at 60 and 90 min, respectively. In conclusion, our data do not support a role for renal kallikrein as a humoral mediator of the natriuretic effect of calcium antagonists, but do not exclude the possibility that ANF might participate in the nifedipine-induced increase in sodium and water excretion.

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↗

PubMed1987

The cat: an animal model for studies of inactive renin.

Inactive renin, prorenin, is found in high concentrations in human plasma. We report herein the characteristics of trypsin-activated inactive renin from cat kidney and plasma. Cat and human plasma inactive renin were activated by similar concentrations of trypsin. As in humans, there was more inactive than active renin in cat plasma; also, inactive renin was low but detectable after nephrectomy. Trypsin-activated renal inactive renin, purified on Cibacron blue agarose and pepstatin-amino-hexyl-Sepharose chromatography, was inhibited by pepstatin and by a renin inhibitor similarly to cat and human active renins. The pH optimum of cat renin was biphasic: the higher peak of active renin was at pH 5.7, whereas that of activated inactive renin was at pH 7.5. As in humans, active and inactive plasma renin increased during sodium depletion and inactive renin increased during beta-adrenergic blockade, while active renin decreased. These results demonstrate that cat inactive renin is similar to human prorenin. Therefore, the cat may be a useful model for the study of prorenin.

Adrenergic beta-Antagonists↗

PubMed1987

Sequential changes in plasma luteinizing hormone and plasma prorenin during the menstrual cycle.

Prorenin, the enzymatically inactive biosynthetic precursor of renin, is secreted by the kidneys. However, the ovaries appear to be the source of the cyclical increase in plasma prorenin that occurs in the middle of the menstrual cycle. In this study we examined the temporal relationship between changes in plasma prorenin and LH in normal women to determine whether ovarian prorenin secretion might be stimulated by LH. Blood was collected from nine normal women daily for 7 days in the midcycle period and from six of them every 8 h on 6 of these days. Time zero was taken as the highest plasma LH value. The initial rise in LH (-24 h) preceded the initial rise in prorenin (-8 h) and the LH peak preceded the prorenin peak by 8-16 h. These sequential increases in plasma LH and prorenin occurred in the presence of high plasma estradiol levels. While LH fell in parallel with estradiol, the prorenin peak was more sustained and plasma prorenin remained above baseline at 40 and 48 h, at a time when both estradiol and LH had reached a new basal level. These results suggest that gonadotropins stimulate ovarian prorenin release. The timing of the changes in plasma prorenin and its presence in high concentrations in ovarian follicular fluid suggest that prorenin may be involved in the process of ovulation. The results also suggest that changes in plasma prorenin may determine the activity of an ovarian renin system that functions independently of circulating active renin.

Adult↗

PubMed1987

Immunoradiometric assay of active renin in human plasma: comparison with plasma renin activity.

The direct measurement of active renin with monoclonal antibodies (IRMA) in plasma from hypertensive patients was compared with the traditional PRA method. Two monoclonal antibodies were used: 3E8 and 4G1. The first was coupled to magnetizable beads and was used to trap both active and inactive renin from plasma. The second antibody, 4G1, was iodinated and used to detect active renin trapped by 3E8. The correlation coefficient between the two methods was very high (r = 0.98, p less than 0.001) in plasma samples whose PRA values were higher than 2 ng/ml/h; in low renin samples (PRA lower than 2 ng/ml/h) no significant correlation was found (r = 0.12 n.s.). When PRA and IRMA were performed before and after trypsin activation of inactive renin, the percentage of inactive over total renin was 86.8% and 84% as calculated with PRA and IRMA respectively. The direct monoclonal antibodies method for measuring active renin can be usefully adopted, in conjunction with the traditional PRA procedure, in studying both clinical and pathophysiological aspects of the renin-angiotensin system.

Antibodies, Monoclonal↗

PubMed1987

Ovarian prorenin.

We review here recent evidence that the ovaries synthesize and secrete prorenin and we explore the possible reasons why prorenin, and not active renin, is formed almost exclusively in this extra-renal site. Very high concentrations of prorenin are present in the human ovary in the fluid inside mature follicles. This ovarian prorenin appears to be secreted into the circulation since plasma prorenin increases in normal women for two to three days at mid-menstrual cycle, at the time of ovulation. No change in plasma active renin occurs at this time. Plasma prorenin increases much more at mid-cycle in women whose ovaries have been hyperstimulated with gonadotropins. Their mid-cycle increment in plasma prorenin (after hCG) is directly related to the number of ovarian follicles. Plasma prorenin also increases markedly (10-fold) in pregnant women within two weeks after conception, in parallel with the rise in endogenous hCG. The ovaries are the apparent source of the increase in plasma prorenin during pregnancy since no such increase occurred in a woman with ovarian failure who conceived after receiving a donor egg. These results suggest that the ovaries synthesize and secrete prorenin in response to stimulation by gonadotropic hormones. Future studies will investigate the potential role of ovarian prorenin in human reproductive function. We postulate the existence of a prorenin receptor which activates prorenin and, in consequence, activates a local renin-angiotensin system. The functioning of this system may be regulated by changes in prorenin and its receptor.

Animals↗

PubMed1987

Comparison of sublingual and oral captopril in hypertension.

The use of sublingual captopril has been recently suggested in hypertensive crisis on the assumption of a faster absorption and thus a more rapid effect on blood pressure than with the oral route. To verify this hypothesis we have compared the hypotensive effect of oral and sublingual captopril in 40 essential hypertensives who were randomly allocated to either route of administration. Captopril was administered orally dissolved in water or allowed to dissolve under the tongue. After 5, 10, 20, 30, 40, 60 and 90 minutes blood pressure, Plasma Renin Activity (PRA) and Angiotensin Converting Enzyme (ACE) were measured. No significant differences were found between the two groups in the time course of blood pressure decrease, PRA increase and ACE inhibition. The changes of the parameters studied was superimposable irrespective of the route of administration thus not supporting the hypothesis that sublingual captopril might be absorbed more rapidly.

Administration, Oral↗

PubMed1987

Relation between urinary kallikrein excretion and blood pressure response to a single oral dose of captopril.

Thirty-one essential hypertensives with normal or low PRA were evaluated before and after a single oral dose (50 mg) of captopril. A significant fall both in systolic and diastolic blood pressure (BP) was obtained in the subgroup of patients who were classified as "normal kallikrein hypertensives", while no significant change in BP was observed in "low kallikrein hypertensives". Furthermore the mean percentage fall in mean BP, throughout the 2 hours following captopril administration, was significantly related to the basal value of urinary kallikrein excretion (r = 0.47 p less than 0.05) in the entire group of patients. Our results suggest that a blunted activity of the kallikrein system might be responsible for failure of captopril in lowering BP in patients in whom the renin-angiotensin system is not pathogenetically implicated.

Adult↗