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Biomedical subjects

A Distler

Publications and source records attributed to A Distler.

At least 163 records · Page 9Linked to original sources
PubMed1988

Functional versus structural changes of forearm vascular resistance in hypertension.

Structural changes in resistance vessels have been considered an important factor in triggering and maintaining chronic hypertension in humans and in experimental animals. To determine whether the increased forearm vascular resistance observed following vasodilator maneuvers in hypertensive patients is predominantly due to structural or to functional changes, we examined the influence of different vasodilator stimuli on forearm blood flow and blood pressure in 22 male patients with established essential hypertension and in 22 age-matched normotensive men (age range, 28-52 years). Blood pressure was measured directly, and blood flow was measured by venous occlusion plethysmography. The maneuvers applied were 1) arterial occlusion combined with handgrip exercise and local heating, 2) intra-arterial infusion of the calcium entry blocker nifedipine, 3) intra-arterial infusion of the nonspecific vasodilator sodium nitroprusside, 4) arterial occlusion initiated after intra-arterial infusion of nifedipine. Vascular resistance during vasodilation induced by arterial occlusion or infusion of nifedipine or sodium nitroprusside remained significantly higher in the hypertensive than in the normotensive subjects. However, the maximal vasodilation achieved by the combination of arterial occlusion and nifedipine resulted in a similar resistance in both groups (1.6 +/- 0.2 in the hypertensive vs 1.4 +/- 0.2 mm Hg/ml/min/100 ml tissue in the normotensive subjects. These data suggest that there is an important functional component of the elevated resistance in patients with essential hypertension.

Adult↗
PubMed1988

24-hour noninvasive oscillometric blood pressure monitoring: evaluation of the antihypertensive circadian profile of nitrendipine.

The understanding of blood pressure (BP) and heart rate (HR) variation, circadian changes, and the responses to nonclinical situations has been improved by automated ambulatory recordings. The antihypertensive efficacy of a once-daily regimen (10/20 mg) of nitrendipine was evaluated in detail using the lightest available portable device equipped with an oscillometric blood pressure (BP) recorder (SpaceLabs 90202, weight 480 g) devoid of any electrode. A good antihypertensive effect throughout the day in 20 outpatients could be demonstrated. No significant change of BP could be found in early morning and wake-up period; HR was not significantly affected after 6 weeks of oral therapy.

Adult↗
PubMed1987

Effects of diltiazem alone and combined with mefruside on cardiovascular response at rest and during exercise, carbohydrate metabolism and serum lipoproteins in patients with systemic hypertension.

The antihypertensive effects of the calcium antagonist diltiazem, both alone and combined with the diuretic mefruside, were assessed over 14 months in 36 patients with essential hypertension. Patients received 180 or 270 mg/day; those with inadequate response were given 270 mg/day plus mefruside, 20 mg/day. Both monotherapy and combination therapy significantly reduced blood pressure (BP) at rest and during exercise. However, adding mefruside did not significantly decrease BP below that achieved with diltiazem alone. After 14 months of therapy, the percentage of responders (patients with at least 10% reduction in diastolic BP at rest) was 64% for all patients, 100% (by definition) for those receiving diltiazem alone and 47% for those receiving the combination. Diltiazem decreased heart rate by 6% (4 beats/min at rest) (p less than 0.05). Combined therapy with mefruside did not further reduce heart rate. There were few adverse effects and no undesirable metabolic effects with either monotherapy or combined therapy. Plasma renin activity, aldosterone levels, carbohydrate metabolism, serum lipoprotein levels and routine laboratory test results were unchanged in both groups at the end of the study. Thus, diltiazem is an effective antihypertensive agent and apparently the combination of diltiazem and mefruside does not potentiate the antihypertensive effect of diltiazem alone during long-term therapy.

Adult↗
PubMed1987

Nifedipine vasodilates human forearm arteries and dorsal hand veins constricted by specific alpha-adrenoceptor stimulation.

1. The local dilative effect of the calcium entry blocker nifedipine on forearm arteries and dorsal hand veins has been studied in 27 healthy male volunteers. 2. Nifedipine induced an increase of blood flow by 1190% (P less than 0.001) in the forearm. 3. The construction of the hand veins induced by stimulation of either postsynaptic alpha 1- or alpha 2-adrenoceptors was reduced (P less than 0.001) by nifedipine. 4. The calcium entry blocker nifedipine is a potent dilator of human forearm arteries as well as of dorsal hand veins.

Adrenergic alpha-Agonists↗
PubMed1987

Effects of acute hypermagnesaemia on intracellular calcium concentration and adrenergic activity.

The effects of acute hypermagnesaemia on intracellular free calcium and adrenergic activity were investigated in six normotensive volunteers given intravenous magnesium sulphate for 3 h. The free calcium concentration in platelets decreased after the first hour of infusion (P less than 0.05), but did not remain significantly depressed after 2 and 3 h of continued infusion. Plasma noradrenaline increased during the infusion (P less than 0.05), with no change in plasma adrenaline. The results demonstrate that the effects of intravenous magnesium sulphate on free intracellular calcium and plasma catecholamines are similar to those described with calcium antagonists.

Adult↗
PubMed1987

Follow-up of a method of twenty-four-hour indirect blood pressure monitoring: evaluation of carvedilol, a new antihypertensive agent.

Indirect automatic 24-hour blood pressure monitoring has been found to be reliable and valid and thus has been introduced for the evaluation of dosage and efficacy of antihypertensive drugs. The present double-blind placebo-controlled randomized long-term study reports the therapeutic results of the oral administration of a new beta-adrenergic blocking agent, carvedilol, with direct vasodilator activity in patients with primary hypertension. The antihypertensive effect was acute at onset and comparable in the supine and standing position judged by casual blood pressure readings. Indirect automatic blood pressure monitoring demonstrated a good antihypertensive effect throughout daily activities after single oral dosage. Despite some technical problems with the apparatus (Pressurometer III, Del Mar Avionics), a circadian pattern could be documented in both untreated and treated patients. Blood pressure and heart rate were normally distributed but less variable during treatment. The long-lasting antihypertensive effect was comparable to the commonly used beta-blocker metoprolol. A significantly reduced awakening blood pressure in the morning may indicate a beneficial effect on a possible prognostic factor in arterial hypertension.

Adult↗
PubMed1987

Circadian antihypertensive profile of carvedilol (BM 14190).

Carvedilol (BM 14190) is a new potent and well-tolerated beta-adrenoceptor antagonist with vasodilating properties. Acute clinical studies have confirmed its efficacy as an antihypertensive agent. The present double-blind, randomized, metoprolol-controlled, long-term study reports the therapeutic results of carvedilol in essential hypertensive patients. Compared with placebo, carvedilol significantly reduces blood pressure after oral administration of 50 mg on a single and twice daily regimen. The antihypertensive effect was acute in onset, comparable in supine and standing position, and exercise-induced hypertension and tachycardia were significantly reduced. Indirect automatic 24 h blood pressure monitoring reliably confirmed clinic blood pressure and demonstrated a good antihypertensive effect of carvedilol after a single oral administration throughout daily activities and sleeping periods.

Adrenergic beta-Antagonists↗
PubMed1987

Effects of reactive hyperemia and nifedipine on forearm vascular resistance in essential hypertension: evidence for functional abnormality.

The aim of this study was to explore whether the increased forearm vascular resistance in patients with essential hypertension is predominantly due to structural or functional changes. We studied 22 male patients with moderate essential hypertension and 22 age- and weight-matched normotensive men (28-52 years). The effects of intraarterially infused nifedipine, reactive hyperemia after 10 min arterial occlusion combined with handgrip exercise and local heating, and arterial occlusion combined with nifedipine on forearm blood flow and blood pressure were investigated in random order. Blood pressure was measured directly in the brachial artery and forearm blood flow by venous occlusion plethysmography. The calculated resistance values reduced by nifedipine or following arterial occlusion remained significantly higher in hypertensives than in normotensives. However, the maximal vasodilation achieved by the combination of arterial occlusion and nifedipine resulted in a similar decrease of resistance in hypertensives and normotensives. These data suggest that there is an important functional component of the elevated vascular resistance in patients with essential hypertension.

Adult↗
PubMed1987

Changes in sensitivity to angiotensin II in platelets.

Our study on intracellular effects of angiotensin II in human platelets showed that: (1) angiotensin II increases intracellular free calcium in platelets via a receptor-operated mechanism and this increase is dose-dependent; (2) the effect on platelet intracellular free calcium depends on the extracellular calcium concentration; (3) ACE inhibition leads to an increased sensitivity of intracellular free calcium to angiotensin II but does not alter epinephrine-induced calcium increase; (4) nifedipine reduces the susceptibility of platelet intracellular free calcium for angiotensin II.

Administration, Oral↗
PubMed1987

Effects of nitrendipine and tiapamil on 45Ca2+ influx and on platelet aggregation.

The effects of the dihydropyridine derivative nitrendipine and of the phenylalkylamine derivative tiapamil on 45Ca2+ influx was determined in platelets in vitro and on platelet aggregation ex vivo. Thrombin-stimulated 45Ca2+ influx was inhibited by 10 mumol/l nitrendipine and 100 mumol/l tiapamil. ADP- and adrenaline-induced platelet aggregation were inhibited in normotensive volunteers following short-term administration of nitrendipine (20 mg b.i.d.) but not after tiapamil (225 mg t.i.d.). Therefore, mechanisms other than the inhibition of Ca2+ influx should be considered to be responsible for inhibition of platelet aggregation by nitrendipine ex vivo.

Adult↗
PubMed1987

Regulation of alpha 2-adrenoceptor density in normotensive and hypertensive man.

We examined normotensive and hypertensive subjects in order to determine whether changes in platelet alpha 2-adrenoceptor density following alterations in plasma noradrenaline are related to changes in noradrenaline (NA) reactivity. Noradrenaline reactivity, plasma NA, alpha 2-adrenoceptor density, and adenylate cyclase activity were measured before and after a 24-h infusion of NA at a subpressor dose (0.02 micrograms/kg per min, n = 13), and also after application of drugs known to increase (nifedipine and furosemide) or decrease (clonidine) plasma NA. Measurements were obtained 60 min after nifedipine (20 mg in a single dose, n = 13), after 3 weeks on furosemide (30 mg twice a day, n = 8) and after 1 week on clonidine (150 micrograms three times a day, n = 5). Infusion of NA decreased alpha 2-adrenoceptor density (P less than 0.01) and NA reactivity (P less than 0.05). Nifedipine decreased alpha 2-adrenoceptor density and NA reactivity (P less than 0.01 for both) in patients with essential hypertension. The alterations in alpha 2-adrenoceptor densities were paralleled by a decreased adrenaline-induced inhibition of adenylate cyclase activity (P less than 0.01). Furosemide decreased alpha 2-adrenoceptor density (P less than 0.01), the fraction of high-affinity binding sites (P less than 0.01) and NA reactivity (P less than 0.05) in normotensive subjects. Following clonidine all three parameters, alpha 2-adrenoceptor density, the fraction of high affinity sites and NA reactivity, increased (P less than 0.05 for each).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1987

Ouabain-induced elevation in forearm vascular resistance, calcium entry and alpha-adrenoceptor blockade, and release and removal of noradrenaline.

The activity of the ouabain-sensitive Na+K+-ATPase may be reduced in primary hypertension by an ouabain-like humoral factor with resultant increase in intracellular Na+ and Ca2+ and peripheral vasoconstriction. To test this, we studied the forearm blood flow in 18 normotensive subjects. First, nifedipine, phentolamine, prazosin, sodium nitroprusside and ouabain were infused into the brachial artery. Secondly, each vasodilator was given in combination with ouabain. Blood pressure was measured directly, and blood flow by venous occlusion plethysmography. When nifedipine was combined with ouabain the elevation of vascular resistance was completely abolished. We detected no effect on the forearm veno-arterial difference for noradrenaline following intra-arterial infusion of drugs. If an ouabain-like factor plays a role in producing the elevated resistance of chronic hypertension, calcium entry blockers will act close to the site of this primary abnormality.

Adrenergic alpha-Antagonists↗
PubMed1987

Vasopressin is increased in mineralocorticoid-induced blood pressure increase in man.

Vasopressin has been studied intensively in DOCA-salt rats and seems to play an important role in this model of hypertension. In the present study we investigated plasma vasopressin in seven normotensive young volunteers during the early phase of mineralocorticoid-induced hypertension. We administered 0.8 mg/day fludrocortisone for 1 week. Body weight, blood pressure, plasma vasopressin, plasma osmolality and electrolytes, as well as plasma renin activity, were evaluated on days 0, 3 and 7. Blood pressure increased significantly from 117/67 to 121/76 mmHg (P less than 0.05) within 1 week, while plasma osmolality remained unaltered at 284 +/- 3 mOsmol/l. Plasma vasopressin (0.45 +/- 0.1 pg/ml) was increased after 3 days (0.68 +/- 0.5 pg/ml) and rose further to 1.53 +/- 0.27 pg/ml after 1 week (P less than 0.05). Changes in plasma vasopressin concentration were not correlated with alterations in blood pressure. Our results show an increase in plasma vasopressin in the early phase of mineralocorticoid-induced hypertension in man. However, the observed increase is moderate and does not seem to explain the increase in blood pressure alone, but could contribute to the blood pressure increase during mineralocorticoid treatment.

Adult↗
PubMed1987

Platelet intracellular free calcium and hypertension.

Platelet intracellular free calcium concentration was assessed by the quin-2 method in 38 patients with essential hypertension and in 35 normotensive subjects. The concentrations were found to be significantly higher in the hypertensive patients (p less than 0.05); however, there was a wide overlap between the values of both groups. In addition, we determined platelet intracellular free calcium in another model of increased blood pressure, the blood pressure elevation following administration of the synthetic mineralocorticoid fludrocortisone. Administration of 0.8 mg fludrocortisone per day to eight normotensive volunteers resulted in a pronounced increase in intracellular free calcium after the first week and a decrease toward control levels thereafter, while blood pressure remained elevated throughout the period of fludrocortisone administration. Our findings suggest that an increase in intracellular free calcium concentration is a transitory phenomenon and not directly related to the blood pressure elevation.

Adult↗