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Biomedical subjects

W Kiowski

Publications and source records attributed to W Kiowski.

At least 163 records · Page 9Linked to original sources
PubMed1985

The adrenaline-alpha 2-adrenoceptor-mediated vasoconstrictor axis.

In patients with essential hypertension plasma adrenaline concentrations have been found to be higher than in normotensive subjects and this may represent increased adrenergic activity. Adrenaline released into the circulation can be taken up by the sympathetic nerve ending and as it is re-released as a co-transmitter it enhances exocytotic noradrenaline release by stimulating prejunctional beta-adrenoceptors and as a consequence it contributes to postjunctional alpha 1-adrenoceptor-induced vasoconstriction. Adrenaline may also induce vasoconstriction via post- and extra-junctional alpha 2-adrenoceptors, as shown by a decrease in the forearm blood flow during adrenaline infusions in the postjunctional alpha 1- and beta-blocked forearm vasculature, an effect that could be antagonized by alpha 2-adrenoceptor blockade with yohimbine. alpha 2-Adrenoceptor stimulation in platelets showed an increased sensitivity to adrenaline, as determined by sensitivity in counteracting the inhibitor effect of PGI2 on intracellular free calcium concentration in untreated patients with essential hypertension, when compared with treated patients or normotensive subjects. As these effects can be normalized by antihypertensive treatment this suggests that the increased hormone sensitivity may be related to the elevated intracellular free calcium concentration. Thus adrenaline, via pre- and post-junctional adrenoceptors, may contribute to enhanced vascular smooth muscle contraction, which most likely is sensitized by the elevated intracellular calcium concentration.

Blood Platelets↗
PubMed1985

Adrenoceptors, calcium, and vasoconstriction in normal and hypertensive humans.

The sympathetic nervous activity contributes to the pathophysiology of essential hypertension in an early phase and in younger patients mainly through increased beta-adrenoceptor-mediated functions and in a later phase and in older patients in whom beta-adrenoceptor-mediated functions are blunted, through increased alpha-adrenoceptor-mediated and calcium-influx-dependent vasoconstriction. Intracellular free calcium concentration is elevated in platelets of hypertensive patients and relates directly to the degree of their blood pressure, likely reflecting increased intracellular calcium concentration in vascular smooth muscle cells. A sympathetic factor is suggested further by the enhanced alpha 1-and alpha 2-adrenoceptor-mediated and calcium influx-dependent, vasoconstriction both of which are normalized by antihypertensive treatment in parallel with a normalization of intracellular free calcium and of the increased adrenaline sensitivity of platelets. The higher sensitivity to adrenaline for thrombin-induced calcium increases in platelets of hypertensive patients indicates potentiation of calcium influx (and mobilization from intracellular stores) by adrenaline, a mechanism that is mediated by alpha 2-adrenoceptors. As this effect is more pronounced in younger patients, increased adenylate cyclase sensitivity may prevail in the early and alterations in calcium influx-dependent mechanisms in the later phase of essential hypertension. The transition into a hypertensive state with reduced-reflex cardiovascular counterregulation codetermines the antihypertensive effectiveness of calcium antagonists in these patients.

Arm↗
PubMed1985

Prejunctional alpha 2-adrenoceptors and norepinephrine release in the forearm of normal humans.

To investigate the prejunctional alpha 2-adrenoceptor-mediated autoinhibitory feedback for norepinephrine (NE) release, we measured the response of forearm blood flow (FAF, mercury in silastic strain gauge plethysmography) and changes of the forearm venous-arterial NE difference (delta VA-NE, deep forearm vein, brachial artery norepinephrine concentration) induced by six intrabrachial artery 5-min infusions of clonidine in 13 normal volunteers. NE spillover into the forearm circulation was estimated as the product of delta VA-NE and FAF after three clonidine infusions. Clonidine caused dose-dependent decreases in FAF with a maximum reduction of FAF after the highest dose of clonidine of 32 +/- 8%, (N = 7, p less than 0.01) indicating postjunctional alpha-adrenergic stimulation. delta VA-NE increased slightly yet calculated norepinephrine spillover remained statistically unchanged after clonidine. The results suggest that auto-inhibitory feedback control of neuronal transmitter release via prejunctional alpha 2-adrenoceptors may not to an important degree modulate norepinephrine release in the forearm vasculature of healthy subjects.

Adult↗
PubMed1985

Antihypertensive treatment using calcium antagonists in combination with captopril rather than diuretics.

The antihypertensive efficacy of combination therapy with the angiotensin-converting enzyme inhibitor captopril and a diuretic or a calcium antagonist was compared in 16 patients with essential hypertension with a blood pressure of over 160/95 mm Hg having triple drug therapy. While monotherapy with a calcium antagonist--usually verapamil 500 mg/day or nitrendipine 70 mg/day--did not reduce diastolic blood pressure to greater than 95 mm Hg, this goal was achieved in 15 out of 16 patients with the combination of captopril (53 mg/day) and the calcium antagonists in the above dose (151 +/- 4/88 +/- 2 SEM mm Hg) and in 13 out of 16 patients with captopril (84 mg/day) and a diuretic (158 +/- 4/91 +/- 1 mm Hg). There was a direct relationship between intraindividual pressure responses to the two drug combinations (r = 0.88, p less than 0.001). Heart rate was similar and weight lower on the captopril-diuretic combination. Captopril's antihypertensive efficacy can be equally enhanced by calcium antagonists (without affecting renin long term) as by diuretics, which are thought to work by stimulating the renin-angiotensin system. The calcium antagonist-captopril combination may be of particular advantage in hypertensive patients who are otherwise difficult to treat.

Adult↗
PubMed1985

Hemodynamic and antihypertensive treatment responses with calcium antagonists.

Calcium antagonists induce vasodilation and a consequent fall in blood pressure that initially is associated with baroreflex-mediated stimulation of the sympathetic nervous and renin-angiotensin system, resulting in increased heart rate and cardiac output. During chronic treatment, baroreflex-mediated stimulatory effects subside, probably because of a resetting of baroreflexes or inhibition of neuronal noradrenaline release. Ultimately, the antihypertensive response is codetermined by the responsiveness of these counterregulatory systems in the individual patient. In older patients who have blunted baroreflex and beta-adrenoceptor-mediated functions, a greater fall in blood pressure results as compared with younger patients in whom counterregulatory reflexes are more vivid. Therefore, older patients respond particularly well to calcium antagonists, whereas younger patients respond better to beta-blockers. In patients with essential hypertension, free cytosolic calcium concentration in platelets is elevated and calcium influx-dependent vasoconstriction is enhanced. Antihypertensive treatment with calcium antagonists and beta-blockers results in a normalization of both calcium influx-dependent vasoconstriction as well as free calcium concentration in platelets. Free cytosolic calcium concentration in platelets may reflect free calcium concentration in vascular smooth muscle cells, its reduction leading to vasodilation and antihypertensive response.

Adrenergic beta-Antagonists↗
PubMed1985

Position of calcium antagonists in antihypertensive therapy.

More than 20 years ago calcium antagonists were shown to lower elevated blood pressure. Today's worldwide recognition, at least in part, is due to rising research interest in cellular ion regulation abnormalities in essential hypertension. Using the human platelet as a model for the vascular smooth muscle cell, a direct relationship was observed between intracellular free calcium concentration and the height of blood pressure before as well as during different antihypertensive treatments. Calcium influx is an important determinant of vasoconstriction, and excess calcium influx-dependent vasoconstriction was shown with plethysmographical studies in patients with essential hypertension. Calcium antagonists acutely lower blood pressure by reducing intracellular calcium and peripheral vascular resistance. The degree of the attendant sympathetic nerve reflex activation and counterregulatory mechanisms codetermine the antihypertensive result of the individual. Chronic monotherapy with calcium antagonists results in an antihypertensive response that is related directly to the patient's age and pretreatment blood pressure and indirectly to renin. These studies led to a new treatment concept: calcium antagonists can be used as alternatives to diuretic drugs primarily in the older and low-renin patients and beta-blockers or converting enzyme inhibitors can be used in the younger or high-renin patients with greater efficacy. With the appropriate choice, calcium antagonists alone or combined with any other antihypertensive drug provide good blood pressure control with little subjective and objective adverse effects.

Adrenergic beta-Antagonists↗
PubMed1985

Hormonal modulation of intracellular free calcium in platelets from normotensive and hypertensive subjects.

Sensitivity to adrenaline-antagonism of the inhibitory effect of PGI2 on thrombin-induced increase in [Ca2+]i was measured in platelets from normotensive and untreated hypertensive subjects. Platelets from hypertensive subjects exhibited an increased sensitivity to adrenaline. This effect was more pronounced in younger patients with hypertension, and suggests an increased adenylate cyclase sensitivity in the early hypertension. The data also indicate that a mechanism linked to calcium-influx plays an important role in older hypertensives. This may explain the greater efficacy of calcium entry blockers in older hypertensive patients with essential hypertension.

Blood Platelets↗
PubMed1984

Use of calcium antagonists as monotherapy in the management of hypertension.

A wide variety of drug treatments are available for the management of hypertension. Often, effective therapy is found only through a process of elimination. A more pathophysiologically oriented method of choosing therapy is based on classification of patients into those with low-, normal-, and high-renin hypertension. In the past, for example, diuretics were considered to be the most effective agents for the treatment of low-renin hypertension. Most cases of essential hypertension are characterized by increased vascular resistance. Calcium channel influx is a major determinant of the free intracellular calcium concentration that finally triggers the contractile process of the vascular smooth muscle cell and thereby determines arterial resistance. In man, free calcium concentration in platelets is closely related to the height of systolic and diastolic blood pressure. Vasodilatation produced by the intra-arterial infusion of a calcium channel blocker into the forearm circulation is significantly greater in hypertensive patients than in normotensive subjects, threefold that observed with sodium nitroprusside, and fourfold that found with prazosin. In hypertensive patients, these effects are correlated directly with plasma epinephrine--reflecting sympathoadrenal activity--and inversely with the activity and reactivity of the renin-angiotensin system. In several clinical studies, the decrease in blood pressure following the administration of calcium channel entry blockers was directly correlated to the patient's age and pretreatment blood pressure, and indirectly to the pretreatment plasma renin activity. The effects of these agents are apparently also comparable to the over-all responses achievable with beta blockers and diuretics. In the future, calcium entry blockers may replace diuretics as first-line therapy for older patients and those with low-renin hypertension.

Calcium↗
PubMed1984

Renin profiling to select antihypertensive baseline drugs. Renin inhibitors for high-renin and calcium entry blockers for low-renin patients.

Renin profiling stimulated research into the pathophysiology of essential hypertension and influenced the development of antihypertensive treatment strategies. Patients with a high renin value and usually younger age respond better to drugs that interfere with the renin-angiotensin system, that is, beta blockers or converting enzyme inhibitors. Patients with a low renin value and often older age respond better to calcium entry blockers or diuretics. Patients with normal renin levels exhibit mixed but, on average, equal responses to these types of drugs. A pathophysiology-oriented antihypertensive treatment strategy is proposed in which beta blockers or converting enzyme inhibitors are used as one and calcium entry blockers--in the place of diuretics when possible--as the other baseline drug, and this approach may provide a cardiac-protective effect.

Adrenergic beta-Antagonists↗
PubMed1984

[Calcium antagonists in the treatment of arterial hypertension. Attempt at a differential therapy].

In the treatment of arterial hypertonia with calcium antagonists good use is made of the vasodilatory effect, which is in the chronic therapy not accompanied by water and volume retention. In three clinical studies it was investigated, which patients could be given a single drug treatment with calcium antagonists. Older patients with a high basal blood pressure and a slight activation of the renin system seem to respond most favourably. Single drug therapy with calcium antagonists is also advantageous for the various illnesses accompanying hypertonia, such as coronary heart disease, cardiac insufficiency, obstructive lung disease or diabetes mellitus.

Adult↗
PubMed1984

High salt intake blunts plasma catecholamine and renin responses to exercise: less suppressive epinephrine in borderline essential hypertension.

Graded physical exercise was associated with a parallel increase in plasma epinephrine and norepinephrine concentrations, and increments in the latter correlated directly with concurrent increases in plasma renin activity, heart rate, and blood pressure as studied in four normal subjects. With a high salt intake, plasma catecholamine levels were lower at each grade of exercise; the norepinephrine-renin response curve was shifted to the right and the norepinephrine-heart rate response curve to the left. In five patients with borderline essential hypertension, after salt loading epinephrine concentrations were higher and their responses during exercise greater than in normal subjects. A high salt intake suppresses the activity of the sympathetic nervous system as well as the renin system but increases cardiovascular responsiveness to pressor hormones. A high dietary salt intake may contribute to elevated concentrations of plasma epinephrine and to its cardiovascular effects in borderline essential hypertension.

Adult↗
PubMed1984

Sympathetic nervous system in essential hypertension and antihypertensive response to alpha 2-adrenoceptor stimulation.

In patients with essential hypertension, the vasodilator response in the forearm circulation to postjunctional alpha 1-adrenoceptor blockade with prazosin is enhanced. Besides the effects at classical postjunctional alpha 1-adrenoceptor, postjunctional alpha 2-adrenoceptor-mediated effects contribute to vascular tone, and these may be comparable in magnitude to those observed with prazosin. Owing to the extrajunctional localization of alpha 2-adrenoceptors, they may be preferential targets for circulating catecholamines and adrenaline in particular. No evidence of autoinhibitory noradrenaline feedback system via prejunctional alpha 2-adrenoceptors was found by measuring noradrenaline release from the forearm. Therefore increased sympathetic nerve activity, as demonstrated by increased plasma adrenaline concentrations, plays an important role in the pathophysiology of essential hypertension by contributing to increased vascular resistance. Central prejunctional alpha 2-adrenoceptor-stimulating drugs lower sympathetic nerve activity and thereby peripheral resistance and blood pressure, and this effect seems to override peripheral (pre-) and postjunctional alpha 2-adrenoceptor-stimulating effects.

Adrenergic alpha-Agonists↗
PubMed1984

Antihypertensive therapy with the long-acting calcium antagonist nitrendipine.

The antihypertensive efficacy of the calcium entry blocker nitrendipine administered as monotherapy (20-80 mg; mean, 36/day) on the average for 144 days to 46 patients with essential hypertension (WHO I and II) was investigated in relation to age, pretreatment blood pressure, and plasma renin activity. In addition, we compared the blood pressure responses to verapamil (n = 11) and nifedipine (n = 15) with those to nitrendipine. Nitrendipine monotherapy reduced blood pressure from 168 +/- 16/107 +/- 7 mm Hg to 145 +/- 13/91 +/- 6 (both p less than 0.001); in 33 of 46 patients a diastolic pressure less than or equal to 95 mm Hg was achieved. During long-term treatment, heart rate and body weight remained unchanged. Thirteen of 16 patients in whom blood pressure was measured 24 h after a single oral dose (20 to 40 mg) reached a diastolic pressure less than or equal to 95 mm Hg. Treatment with nitrendipine had to be discontinued because of severe headache in two and ankle oedema in one patient. The fall in mean blood pressure after nitrendipine was directly related to age (r = 0.553; p less than 0.001) and pretreatment mean blood pressure (r = 0.470; p less than 0.01) and inversely related to plasma renin activity (r = 0.558; p less than 0.001). These correlations were also significant for systolic and diastolic blood pressure. There was comparable antihypertensive efficacy, as expressed by changes in mean blood pressure, between nitrendipine and verapamil (r = 0.869; p less than 0.01), and nitrendipine and nifedipine (r = 0.953; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Parallel reduction of calcium-influx-dependent vasoconstriction and platelet-free calcium concentration with calcium entry and beta-adrenoceptor blockade.

In essential hypertension, calcium-influx-dependent vasoconstriction is enhanced, and free calcium concentration in platelets is elevated. To investigate calcium-influx-dependent vasoconstriction as related to platelet calcium concentration blood pressure, forearm blood flow (FAF) and free calcium concentration in platelets were measured in five patients with essential hypertension before and after a 6-week treatment with nitrendipine or acebutolol. Starting from comparable basal values, the increase in FAF (ml/min/100 ml tissue) to intraarterially infused nitrendipine (20 micrograms/100 ml tissue) was 40.7 +/- 6.1 before and 30.7 +/- 12.3 after chronic nitrendipine treatment (p less than 0.05) and 41.6 +/- 6.2 before and 34.6 +/- 14.9 after chronic acebutolol treatment. The "nonspecific" vasodilator response to intraarterial sodium nitroprusside or to postischaemic reperfusion were similar before and during treatment. Platelet-free calcium concentration fell on nitrendipine (p less than 0.05) and on acebutolol (p less than 0.01) treatment. Antihypertensive treatment with calcium entry as well as beta-adrenoceptor blockade resulted in a reduction of calcium-influx-dependent vasoconstriction and a fall in free calcium concentration in platelets. Thus, increased calcium platelets may reflect increased calcium in vascular smooth muscle cells and arteriolar tone.

Acebutolol↗
PubMed1984

Adrenaline induces vasoconstriction through post-junctional alpha 2 adrenoceptors and this response is enhanced in patients with essential hypertension.

The role of adrenaline-induced postjunctional alpha 2 adrenoceptor-mediated vasoconstriction was studied in seven patients with essential hypertension (EHT) and eight normotensive subjects (NT) using forearm venous occlusion plethysmography. Adrenaline (0.01 to 0.08 micrograms/min/100 ml of tissue) infused into the forearm circulation via the brachial artery during alpha l adrenoceptor blockade with prazosin (0.05 micrograms/min/100 ml of tissue) and beta adrenoceptor blockade with propranolol (2 micrograms/min/100 ml of tissue) decreased forearm blood flow (FAF) dose-dependently below basal FAF (P less than 0.001). The adrenaline-induced decrease in FAF was greater in EHT than in NT (P less than 0.01) and was blocked in both groups by alpha 2 adrenoceptor blockade with yohimbine (30 micrograms/min/100 ml of tissue). The increase in FAF following postjunctional alpha-2 blockade as well as following postjunctional alpha-1 blockade was greater in EHT than in NT (P less than 0.01) but was similar in both groups following 'non-specific' vasodilation with sodium nitroprusside. Postjunctional alpha 1 and alpha 2 adrenoceptor-mediated vasoconstriction is enhanced in patients with essential hypertension. Adrenaline induced postjunctional alpha 2 adrenoceptor-mediated vasoconstriction could contribute to elevated vascular resistance in patients with EHT and elevated plasma adrenaline concentrations particularly in the presence of blunted beta adrenoceptor-mediated functions.

Adult↗
PubMed1984

Forearm vasoconstrictor response to ouabain: studies in patients with mild and moderate essential hypertension.

The dependence of arteriolar vasoconstrictor tone on the activity of Na+,K+-ATPase was studied in 17 normotensive subjects (NT) and 28 patients with essential hypertension (EH) by measuring the response in forearm blood flow and vascular resistance to intraarterial infusion of the Na+,K+-ATPase inhibitor ouabain. Basal plasma aldosterone concentrations were elevated in mild (n = 14) and moderate (n = 14) EH patients as compared with NT (p less than 0.001 for both) and correlated positively with intraarterial diastolic blood pressure (r = 0.551, p less than 0.001). Ouabain in incremental doses of 0.4-16 micrograms/100 ml tissue induced a vasoconstrictor response in the forearm with a maximal effect to 8 micrograms/100 ml tissue, which was not associated with an increase in regional noradrenaline release. The vasoconstrictor response to ouabain, 8 micrograms/100 ml, expressed as the percentage change in the ratio of forearm vascular resistance (FR) on the experimental side versus the control side, was 29.6 +/- 6.8% in NT (p less than 0.001); 51.9 +/- 8.4% in mild EH (p less than 0.001), and 36.0 +/- 12.7% in moderate EH (p less than 0.05). The vasoconstrictor response was greater (p less than 0.05) in patients with mild EH than in NT but did not differ in NT and patients with moderate EH. Vascular reactivity in the forearm, as assessed by intraarterial infusions of noradrenaline (3, 8, and 20 ng/min/100 ml tissue), did not differ in NT (n = 9) and patients with mild (n = 9) or moderate (n = 9) EH. The results suggest increased activity of arteriolar Na+,K+-ATPase in mild EH, which may represent a mechanism counteracting an accumulation of intracellular sodium and thereby an early increase in forearm vascular resistance (FR).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗