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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Aminoglycoside dosage in hemodialysis patients.

Regulating aminoglycoside dosage in patients undergoing hemodialysis is difficult because its elimination depends entirely on renal function and because the therapeutic margin is narrow. Guidelines for aminoglycoside dosage were derived from published population-based kinetics and investigated in a prospective clinical study over a 12-month period in 50 consecutive patients undergoing hemodialysis with acute (70%) or chronic (30%) renal failure. Based on body weight, each patient received one loading dose (1.

Humoral and blood pressure effects of the angiotensin converting enzyme inhibitor ramipril in essential hypertension.

The humoral and antihypertensive activities of the angiotensin converting enzyme (ACE) inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S, 3S, 5S)-2-azabicyclo[3.3.0] octane-3-carboxylic acid (ramipril, Hoe 498) were investigated in 10 patients with essential hypertension (WHO stage I or II).

Antihypertensive and metabolic effects of diltiazem and nifedipine.

The antihypertensive effect of diltiazem (180-270 mg/day) and nifedipine (40-60 mg/day) in slow-release forms was assessed over 8 weeks in a double-blind parallel study in 40 subjects with essential hypertension at rest and during exercise. Blood pressure was comparably reduced in both groups at rest as well as during exercise. The responder rates (greater than or equal to 10% reduction in diastolic blood pressure) after 8 weeks of therapy were 53% at rest and 75% during exercise in the diltiazem group and 78% and 50%, respectively, in the nifedipine group.

Double-blind comparison of the cardioselective beta-blockers bisoprolol and atenolol in hypertension: the Bisoprolol International Multicenter Study (BIMS).

The antihypertensive efficacy and tolerability of bisoprolol and atenolol were compared in the Bisoprolol International Multicenter Study (BIMS). In 104 patients with essential hypertension (21 to 70 years of age and diastolic blood pressures (DBP) of 100-120 mm Hg in the sitting position), after a four-week placebo period, the active drug was given in a random double-blind crossover design (10 to 20 mg bisoprolol, 50 to 100 mg atenolol) for eight weeks each, with a 2 to 6 week placebo wash-out phase between active therapy. All blood pressures were recorded 24 h after drug intake.

Sympathetic tone and pressor response to noradrenaline during mineralocorticoid-induced blood pressure rise in man.

To gain insight into the role of the sympathetic nervous system in the development of mineralocorticoid hypertension, we determined noradrenaline and adrenaline in plasma and urine before, during and after administration of the synthetic steroid, fludrocortisone, for a period of 6 weeks in normotensive volunteer subjects. In addition, pressor reactivity to exogenous noradrenaline, platelet alpha 2- and lymphocyte beta 2-receptors, and platelet intracellular free calcium were determined. Fludrocortisone induced a fall in free and sulpho-conjugated plasma noradrenaline and after 6 weeks, a rise in free and sulpho-conjugated noradrenaline excretion.

Specific alpha-adrenoceptor-mediated vasoconstriction in human veins and interaction with the calcium entry blockers nifedipine and diltiazem.

In order to characterize the pharmacological properties of post-junctional alpha-adrenoceptors, the vasoconstricting effects of the non-specific alpha-adrenoceptor agonist noradrenaline, of the specific alpha 1-adrenoceptor agonist phenylephrine and of the specific alpha 2-adrenoceptor agonist azepexole and the interaction with the calcium entry blockers nifedipine and diltiazem were studied in hand veins of eight healthy volunteers. Both subtypes of alpha-adrenoceptors could be demonstrated in human hand veins in vivo. The alpha 1-subtype seemed to prevail.

Intracellular free calcium and ionized plasma calcium during mineralocorticoid-induced blood pressure increase in man.

Intracellular free calcium is considered to play a key role in vascular smooth muscle contraction. Platelet-free intracellular and plasma total and ionized calcium were assessed during mineralocorticoid-induced blood pressure increase in eight normotensive subjects receiving 0.8 mg fludrocortisone per day for 6 weeks.