Biomedical subjects

P Dessi'-Fulgheri

Publications and source records attributed to P Dessi'-Fulgheri.

8 recordsLinked to original sources

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

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

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 effects of aprotinin, a glandular 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 Na intake. Aprotinin (1 x 10(6) KIU) or Saline (200 ml) were infused in all patients for 6 hrs. Blood samples were taken for plasma renin activity (PRA) and 6-hr urine collections were obtained for active and inactive kallikrein, Na+, K+, Cl-, Ca++ excretion measurements. In patients on unrestricted sodium diet aprotinin had no effect on 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 percent 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 low sodium diet. Aprotinin reduced the urinary excretion of active kallikrein by 81% and the active to total kallikrein ratio from 24% to 6%, suggesting that it could interfere with the in-vivo activation of inactive kallikrein. 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↗

PubMed1983

Trypsin-activatable inactive renin in rat plasma.

1. Activation of inactive renin in rat plasma has been studied with different trypsin concentrations and incubation times at pH 6.2 and 4 degrees C. 2. Trypsin concentrations below 2 mg/ml, lower than endogenous rat plasma anti-trypsin activity, do not activate inactive renin, whereas maximal activation is obtained with trypsin at 6 mg/ml for 1 min at 4 degrees C, pH 6.2. 3. Under these conditions trypsin can cleave dialysable fragments from renin substrate. ANG I can be generated at 37 degrees C with a pH optimum of 5.3. Nevertheless, the ANG I formation at pH 6.2 was totally unaffected. 4. Incubations longer than 2 min with trypsin at 6 mg/ml can induce a direct cleavage of dialysable ANG I-containing fragments strongly interfering with the measurements of renin activity at pH 6.2. 5. On average 40% of the total renin measured in plasma of normotensive WK rats is in the inactive form, although a wide range of variation is observed.

Angiotensin I↗

PubMed1981

Optimum tryptic activation of inactive renin in human plasma is independent of endogenous anti-tryptic activity.

1. Plasma samples from 31 normal subjects were treated (at 4 degrees C, pH 7.0, for 2 min) with different concentrations of trypsin (500, 1000, 2000, 3000 and 4000 microgram/ml) in order to assess which concentration yielded the maximum activation of inactive renin. 2. Endogenous antitryptic activity was also measured in all samples; the mean value +/- SD (in microgram of trypsin inhibited by 1 ml of plasma) was 953 +/- 550 microgram/ml (range 34-1800 microgram/ml). 3. In the entire group of subjects the values of trypsin-activated renin measured with trypsin at 2000 microgram/ml were significantly higher than those obtained with lower or higher trypsin concentrations. 4. With subjects divided into subgroups according to their endogenous anti-tryptic activity, the maximum yield of activation was reached with trypsin at 2000 microgram/ml. 5. No significant correlations were found between single values of active, inactive or trypsin-activated renin and the corresponding levels of endogenous anti-tryptic activity. However, a weak but significant correlation (r = 0.39, P less than 0.05) was found between single values of anti-tryptic activity and the corresponding percentage of activation of inactive renin. 6. Thus the maximum activation of inactive renin at 4 degrees C for 2 min is obtained with trypsin at 2000 microgram/ml independently of the corresponding endogenous anti-tryptic activity. It is not excluded that the content of protease inhibitors in human plasma might affect the proportion in vivo of circulating active and inactive renin.

Adult↗

PubMed1978

Effects of levodopa alone and in combination with dopa-decarboxylase inhibitors on plasma renin activity in patients with Parkinson's disease.

Plasma renin activity (PRA) of patients with Parkinson's disease was measured in recumbency, upright position, and after frusemide administration. The results show that the renin responses to both stimuli are significantly reduced as compared with those obtained in a group of normal subjects, while recumbent PRA levels of Parkinsonism patients are not significantly lower than those found in recumbent normal subjects. Levodopa treatment, alone or in combination with two different dopa-decarboxylase inhibitors, benserazide and carbidopa, does not modify the renin response to posture or to frusemide. Although the reduced activity of the renin-angiotensin system can play some role in the genesis of orthostatic hypotensive episodes encountered in patients with Parkinsonism, the greater incidence of orthostatis hypotension in patients treated with levodopa seems to be unrelated to any effect of this drug on the renin release.

Adult↗