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Biomedical subjects

A Overlack

Publications and source records attributed to A Overlack.

At least 73 records · Page 4Linked to original sources
PubMed1985

The influence of food intake on pharmacodynamics and plasma concentration of captopril.

The influence of food intake on the acute haemodynamic and humoral effects of captopril has been investigated. Eighteen patients with mild-to-moderate essential hypertension (diastolic blood pressure 95-115 mmHg) were treated in a randomized crossover study with a single oral dose of 25 mg captopril after 2 weeks of placebo. They were randomized to receive captopril either 1 h before or together with a standardized breakfast. Blood pressure, heart rate and plasma concentrations of angiotensin converting enzyme (ACE), angiotensin II (ANG II) and captopril were measured before and every 30 min up to 4 h after drug administration. Angiotensin converting enzyme was significantly more suppressed and plasma concentrations of captopril were significantly higher when the drug was given in the fasting patients. However, there was no significant difference in blood pressure reduction whether captopril was administered in the fasting patients or together with food. The results indicate that the antihypertensive efficacy of captopril is not markedly affected when the drug is administered with food.

Adult↗
PubMed1984

Effects of potassium on blood pressure regulation.

Short-term changes (1 week) of potassium intake had no effect on elevated or normal blood pressure of 18 subjects. Potassium supplementation (100 mmol KCl/day) for 8 weeks caused a fall in blood pressure in 16 patients with mild hypertension. After cessation of potassium supplementation, blood pressure returned to "prepotassium" levels. In healthy volunteers, high potassium intake for 1 week resulted in a marked increase in intraleukocytic concentration of potassium. No change was observed in mean arterial pressure, cardiac index, or total peripheral resistance. The hemodynamic response to an intravenous infusion of ouabain was reduced during high potassium intake. Baroreceptor sensitivity rose during high potassium intake as demonstrated by the infusion of norepinephrine.

Aldosterone↗
PubMed1983

Converting enzyme activity and essential hypertension.

Serum ACE-activity was studied in 27 young patients with uncomplicated essential hypertension. The possible importance of an increase in ACE for the pathogenesis of essential hypertension was evaluated by comparing the ACE levels to PRA, the plasma concentrations of angiotensin II and to the blood pressure lowering effect of captopril. Mean ACE-activity was slightly but significantly elevated in the hypertensive patients when compared to 28 normotensive control subjects. ACE-activity was not correlated to PRA, angiotensin II or the decrease in blood pressure following captopril. It is concluded that the increase in ACE-activity in essential hypertension is not of pathophysiological or clinical significance.

Administration, Oral↗
PubMed1983

Intestinal absorption of glandular kallikrein in the rat.

We studied the possibility of intestinal absorption of glandular kallikrein in unanesthetized rats after administration of 5 mg of active or phenylmethylsulfonyl fluoride-inactivated pig pancreatic kallikrein (PPK). Immunoreactive PPK was measured in plasma and urine by radioimmunoassay using an antiserum to PPK that does not cross-react with rat glandular kallikrein. In addition, we studied the effect of intestinally administered active PPK on the intestinal blood flow distribution. Although immunoreactive PPK could not be detected (less than 10 ng/ml) in plasma after active PPK was administered, very small amounts were found in urine (20-40 ng/3 h). In the urine most of the PPK was in active form because over 75% could be bound to aprotinin-Sepharose. After inactive PPK was administered, immunoreactive PPK was detectable in the plasma of all rats, and urinary excretion was higher than after administration of active PPK. Blood flow distribution to the small intestine as a percentage of cardiac output was significantly greater 30 min after intestinal application of active PPK (5 mg) than after administration of the vehicle alone (1 ml of 0.9% saline). These results suggest that active and inactive PPK is absorbed from the gut in very small amounts. The finding of higher amounts of immunoreactive PPK in plasma and urine after inactive PPK was administered is probably due to the fact that the inactive form of the enzyme is not bound by the plasma inhibitors. These small amounts of kallikrein absorbed appear to have some effect on intestinal blood flow distribution.

Animals↗
PubMed1982

Interactions of diuretics with the renal kallikrein-kinin and prostaglandin systems.

The renal kallikrein-kinin system may participate in the diuretic, natriuretic and antihypertensive effect of diuretics. This possibility was investigated by studying the influence of hydrochlorothiazide on blood pressure and urinary kallikrein excretion in patients with essential hypertension. Furthermore, the effect of kallikrein-blockade and prostaglandin-synthesis inhibition on the acute furosemide-induced changes of diuresis, natriuresis, GFR and renal plasma flow were studied in normotensive subjects. Thiazide treatment normalized the reduced kallikrein excretion of the hypertensive patients. The fall in mean arterial blood pressure was significantly correlated with the increase in urinary kallikrein excretion. In the normotensive subjects aprotinin-induced kallikrein inhibition failed to alter the acute response to furosemide, whereas indomethacin attenuated the diuretic and natriuretic effect of furosemide. The combination of indomethacin and aprotinin had a greater suppressive effect on plasma renin activity than indomethacin alone, suggesting a participation of kallikrein in renin release. An increase in the activity of the renal kallikrein-kinin system may contribute to the long-term antihypertensive effect of thiazide diuretics but it does not seem to be involved in the acute renal responses to furosemide.

Adult↗
PubMed1982

Long-term efficacy of angiotensin-converting-enzyme inhibition with captopril in mild-to-moderate essential hypertension.

1 Thirty-one patients with mild-to-moderate essential hypertension were treated with captopril for 30 months. 2 Captopril effectively lowered raised blood pressure in hypertensive patients with high, low, and normal renin concentrations. There was no significant change in heart rates. Captopril alone normalised blood pressure (diastolic pressure below 95 mm Hg) in 11 patients. In the other patients the addition of hydrochlorothiazide produced a further hypotensive effect. Blood pressure control could be maintained without any signs of tachyphylaxis. 3 Plasma concentrations of aldosterone and angiotensin II were significantly lower after 30 months of therapy than pretreatment values whether captopril was associated with diuretics or not. No relevant symptomatic or biochemical adverse reactions were observed. 4 These data establish the long-term potential of captopril for outpatient therapy in mild-to-moderate forms of essential hypertension.

Adult↗
PubMed1981

Evidence for participation of kinins in the antihypertensive effect of converting enzyme inhibition.

In low- and normal- renin hypertensive patients, but not in high-renin patients, the acute antihypertensive response to the angiotensin-converting enzyme (ACE) inhibitor captopril was completely blocked by aprotinin-induced kallikrein inhibition. Blood pressure reduction with long-term ACE inhibition could be overcome only in part by aprotinin. It is proposed that in low- and normal-renin hypertension the vasodepressor effect of acute ACE inhibition is mainly due to kinin accumulation. Conversely, in high-renin patients a fall in angiotensin II concentration accounts for the hypotensive response to captopril. From the pressor effect of aprotinin in chronically captopril treated patients it appears that kinins are also involved in the blood pressure reduction with long-term ACE inhibition. The finding that ACE inhibition and kallikrein blockade produced predictable and opposite effects on blood pressure suggests broad participation of changes in depressor kinin production in the control of vascular tone in essential hypertension.

Adult↗
PubMed1981

Renal prostaglandins and water balance: studies in normal volunteer subjects and in patients with central diabetes insipidus.

1. In six healthy volunteer subjects polydipsic water loading significantly increased urine volume from 1203 +/- 242 (SEM) to 5072 +/- 320 ml/24 h (P less than 0.001) with a significant decrease in urinary osmolality. This increase in urine volume by more than fourfold was associated with a slight increase in urinary excretion of prostaglandin E2 from 466 +/- 66 to 1017 +/- 174 pmol/24 h (P = 0.05). 2. In five patients with central diabetes insipidus mean urine volume of 10 838 +/- 107 ml/24 h was reduced to 1205 +/- 204 ml/24 h (P less than 0.001) by treatment with 1-desamino-8-arginine vasopressin (desamino-[Arg8]vasopressin; 15 microgram/day) with a significant rise in urinary osmolality. Desamino-[Arg8]vasopressin treatment was associated with a significant increase of suppressed urinary excretion of prostaglandin E2 (PGE2) in four of these patients from 246 +/- 66 to 2643 +/- 677 pmol/24 h (P less than 0.01). 3. Concomitant treatment with indomethacin in addition to desamino-[Arg8]vasopressin significantly suppressed urinary excretion of PGE2 and significantly increased urinary osmolality as compared with treatment with desamino-[Arg8]vasopressin alone. 4. Desamino-[Arg8]vasopressin significantly increased urinary excretion of adenosine 3':5'-cyclic monophosphate (cyclic AMP). However, there was no further change in urinary excretion of cyclic AMP during concomitant indomethacin treatment. 5. The results suggest that urine flow itself is not an important determinant of urinary PGE2 excretion. In patients with central diabetes insipidus the urinary concentrating response to desamino-[Arg8]vasopressin is enhanced during inhibition of prostaglandin synthesis without changes in urinary excretion of cyclic AMP.

Adult↗
PubMed1981

Effect of captopril and aprotinin on inactive renin.

Inactive renin (prorenin) was measured in plasma from untreated hypertensive patients after acute (60 min) administration of the angiotensin I converting enzyme inhibitor captopril, after 4 weeks of treatment with captopril, and after an acute infusion of the protease inhibitor aprotinin. Inactive renin was unchanged during acute captopril therapy despite a 4-fold increase in active renin. In contrast, after 4 weeks of treatment with captopril, inactive renin had increased 2-fold and active renin was also elevated, but to a greater degree (6-fold). Active renin was significantly suppressed by the aprotinin infusion, to about 25%, but the inactive plasma renin level was apparently unchanged. These studies demonstrate that the time course of the responses of active and inactive plasma renins are different; the inactive renin level seems to change more slowly than does active renin in response to the same stimulus. The results also show that a neutral serine protease inhibitor can rapidly reduce the circulating level of active renin. This observation is consistent with the possibility, but does not prove it, that a kallikrein-like enzyme normally activating prorenin was inhibited by aprotinin.

Aprotinin↗
PubMed1980

[Pseudohyponatremia in multiple myeloma (author's transl)].

In the present study frequency and mechanisms of alterations in serum electrolytes in multiple myeloma were investigated. Asymptomatic hyponatremia (up to 93 mmol/l) was present in 7 of 15 patients. Water of serum was significantly lower, viscosity of serum significantly raised as compared to healthy controls. A highly significant negative correlation between sodium concentration and viscosity was found. By measuring serum sodium concentration with viscosity independent dilution systems it could be proved that in each case the observed hyponatremia was caused by flaws in our routinely used viscosity dependent dilution method. The decrease in water of serum contributed only little to the development of hyponatremia. It is concluded that the decrease in serum sodium concentration in multiple myeloma is nothing else than a feigned hyponatremia which needs no therapy.

Aged↗
PubMed1980

[A new principle in long-term treatment of essential hypertension: angiotensin-converting enzyme inhibition (author's transl)].

The blood pressure lowering effect of the orally effective converting-enzyme-inhibitor captopril (SQ 14.225) was investigated in a double-blind study in 20 patients with moderate essential hypertension. During treatment with captopril alone (150 mg t.i.c.) blood pressure dropped from an average of 167/111 to 148/99 mm Hg lying and from 164/113 to 143/99 mm Hg upright whereby 4 patients showed normalisation of their blood pressure (less than 145/95 mm Hg). There was no significant change of pulse frequency. Addition of hydrochlorothiazide led to return to normal of blood pressure in all patients. Even after 6 months of treatment tolerance had not developed. The antihypertensive effect of captopril alone paralleled the one of hydrochlorothiazide and there were no side effects. Activity of the converting enzyme in serum as well as plasma concentrations of angiotensin II and aldosterone were clearly lowered by captopril whereas plasma renin activity increased significantly. Renal sodium and water excretion and glomerular filtration rate were not influenced.

Adult↗
PubMed1980

Decreased urinary kallikrein activity and elevated blood pressure normalized by orally applied kallikrein in essential hypertension.

Urinary kallikrein excretion was significantly lower in patients with essential hypertension (0.48 +/- 0.05 EU/24 h) than in normotensive controls (1.26 +/- 0.14 EU/24 h). Oral administration of hog pancreatic kallikrein normalized decreased urinary kallikrein and reduced arterial pressure. The treatment-induced rise in urinary kallikrein was due to an enhanced release of endogenous enzyme, as was determined by radioimmunoassay. It is proposed that in the hypertensive patients the low urinary kallikrein excretion reflects a defect in renal kallikrein formation which is normalized by oral kallikrein. The hypotensive action of oral kallikrein as well as its stimulating effects on renal kallikrein release suggest that the kallikrein-kinin system is involved in blood pressure regulation and that impaired renal kallikrein activity may be a factor in the maintenance of essential hypertension.

Adult↗
PubMed1980

Impaired renal kallikrein activity and elevated blood pressure normalized by orally applied kallikrein in essential hypertension.

Urinary kallikrein excretion was significantly lower in patients with essential hypertension (0.48 +/- 0.05 EU/24 h) than in normotensive controls (1.26 +/- 0.14 EU/24 h). Oral administration of hog pancreatic kallikrein normalized decreased urinary kallikrein and reduced arterial pressure. The treatment-induced rise in urinary kallikrein was due to an enhanced release of endogenous enzyme, as was determined by radioimmunoassay. It is proposed that in the hypertensive patients the low urinary kallikrein excretion reflects a defect in renal kallikrein formation which is normalized by oral kallikrein. The hypotensive action of oral kallikrein, as well as its stimulating effects on renal kallikrein release, suggest that the kallikrein-kinin system is involved in blood pressure regulation and that impaired renal kallikrein activity may be a factor in the maintenance of essential hypertension.

Administration, Oral↗
PubMed1980

Altered blood pressure and renin responses to converting enzyme inhibition after aprotinin-induced kallikrein-kinin-system blockade.

1. The effect of aprotinin-induced blockade of the kallikrein-kinin system on haemodynamic and biochemical responses to converting enzyme inhibition by SQ 14 225 was evaluated in 26 patients with essential hypertension. 2. SQ 14 225 lowered blood pressure in high, normal and low renin hypertension. In low and normal renin patients, but not in high renin patients, the acute blood pressure-lowering effect of SQ 14225 could be overcome by aprotinin. Aprotinin infusion produced small vasopressor effects in all groups of patients. 3. Aprotinin lowered the level of circulating active renin but not that of inactive renin. 4. It is concluded that in low and normal, but not in high, renin hypertensive patients activation of the kallikrein-kinin system is responsible for the acute blood pressure reduction observed with converting enzyme inhibitions. 3. Aprotinin lowered the level of circulating active renin but not that of inactive renin. 4. It is concluded that in low and normal, but not in high, renin hypertensive patients activation of the kallikrein-kinin system is responsible for the acute blood pressure reduction observed with converting enzyme inhibition. 5. With long-term converting enzyme inhibition kallikrein-kinin system activation seems to play only a minor role. 6. The kallikrein-kinin system may be involved in the regulation of blood pressure. 7. There is no direct evidence of a participation of kallikrein in the activation of prorenin in vivo.

Aldosterone↗
PubMed1980

Evaluation of long-term treatment of essential hypertension with guanfacine.

1. Twenty-two patients with moderately severe essential hypertension were treated for a period of 12 months with guanfacine (BS 100-141), a new centrally-acting antihypertensive agent. A twice daily schedule was followed and the dose range of guanfacine was 1-8 mg daily. 2. In twenty patients satisfactory blood pressure responses (diastolic pressure below 95 mmHg) were achieved in both the supine and the standing position. Pulse rate decreased slightly, though not significantly. 3. Tolerance to the pressure-lowering effect of the drug developed during the third or fourth month of therapy. This could be overcome by either increasing dosage or adding a diuretic. 4. All patients reported side-effects, mainly dryness of the mouth and fatigue. These side-effects became less or disappeared at the end of 3 months. Rebound hypertension on discontinuation of therapy occurred in two patients. 5. Plasma concentrations of noradrenaline and adrenaline as well as plasma renin activity were decreased after 1 week of treatment with the drug. 6. Guanfacine in conjunction with a diuretic is a useful drug in the long-term treatment of hypertension. Reduced central sympathetic outflow may be the major mechanism underlying the antihypertensive effect of the drug.

Adult↗