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Biomedical subjects

W Kiowski

Publications and source records attributed to W Kiowski.

195 records · Page 11Linked to original sources
PubMed1979

Effect of systemic autonomic inhibition on the hemodynamic response to antihypertensive therapy with timolol.

To evaluate the role of systemic autonomic tone in the hemodynamic response to beta-inhibitors, the hemodynamic effects of long-term timolol therapy were studied in hypertensive patients under two sets of conditions: at rest and after pharmacologic systemic autonomic inhibition (SAI). Hemodynamic studies were performed in every subject at the end of a 4-week placebo period and again at the end of a 9-week treatment period. The antihypertensive effect of timolol was associated with decreased cardiac output and unchanged peripheral resistance at rest and with unchanged cardiac output and decreased peripheral resistance after SAI. The hemodynamic response to SAI during the two studies was also markedly different. The findings provide evidence of increased alpha-adrenergic component of systemic autonomic tone during long-term therapy with timolol.

Adult↗
PubMed1978

Renin response to stimulation of cardiopulmonary mechanoreceptors in man.

Plasma renin activity (renin) and hemodynamic response to venous pooling of blood in legs were studied in 24 healthy volunteers and four patients who after bilateral nephrectomy received a functioning renal transplant. Blood pressure cuffs were placed around subjects' thighs and inflated at a pressure 5 mm Hg below the individuals' diastolic pressures. 30 min after thigh cuff inflation, renin significantly increased in all volunteers (mean = 125%). Inflation of cuffs induced a decrease of right atrial pressure, cardiopulmonary blood volume, and cardiac output, but there were no changes in the extra-arterial systolic and diatoloic pressure or in the pressure amplitude. After cuffs were deflated, renin and hemodynamic parameters returned toward normal. In nine volunteers in whom thigh cuff inflation initially elicited renin increases, subsequent intravenous propranolol (0.25 mg/kg) abolished the response to repeated cuff inflation. The renin increase to thigh cuff inflation was absent or suppressed in four patients with a recently transplanted denervated kidney. It is concluded that thigh cuff inflation elicited a reflex-mediated renin increase, and that the reflex stemmed from stimulation of cardiopulmonary mechanoreceptors.

Adolescent↗
PubMed1977

Effect of beta adrenoceptor antagonists on baroreceptor reflex sensitivity in hypertension.

High-pressure baroreceptor reflex sensitivity (BRS) was estimated by measuring the reflex heart rate response to pharmacologic elevation of blood pressure (phenylephrine, 150 to 200 microgram intravenously) in 18 patients with essential hypertension on two occasions: after a 4-wk placebo period and after 9 wk of incremental doses of oral timolol (20, 40, and 60 mg daily). On placebo, measurements were performed both before and after propranolol (0.2 mg/kg intravenously). The level of cardiac vagal inhibition, estimated by the heart rate change after atropine (0.04 mg/kg intravenously), was similar in placebo and on timolol, thereby permitting comparisons of BRS. BRS on placebo (before and after propranolol) correlated with BRS on timolol ( r = 0.87 and 0.90, p less than 0.001), attesting to the reproducibility of BRS measurements. BRS was unchanged by either short-term (propranolol) or long-term (timolol) beta adrenoceptor inhibition. Results were similar in responders (n = 10), whose mean arterial blood pressure on timolol fell by 10 mm Hg or more, and in nonresponders. The findings do not provide evidence for a change in gain of the baroreceptor reflex arc under conditions of short- or long-term beta adrenoceptor inhibition.

Adult↗
PubMed1975

Studies on the chemistry of arterial wall, XVII. Metabolic characteristics of different types of chondroitin sulfate-dermatan sulfate hybrids in arterial tissue.

1) Chondroitin sulfate and dermatan sulfate of bovine arterial tissue exist as copolymers with a varying degree of hybridization between chondroitin and dermatan sulfates. A fraction rich in dermatan sulfate hybridized with 20% chondroitin sulfate (termed DS-rich hybrid) and a fraction rich in chondroitin sulfate containing 17% DS as copolymer constituent (CS-rich hybrid) can be isolated by the subfractionation of the arterial tissue CS-DS preparation. 2) When arterial tissue segments were preincubated with [14C]glucosamine, 95% of the radioactivity incorporated into the glycosaminoglycans was found to be present in the galactosamine moiety of all of the CS-DS subfractions, whereas the relative proportion of 14C radioactivity incorporated into the galactosamine and uronic acid components was 51:49 following preincubation with [14C]glucose. In both experiments the specific radioactivity of the DS-rich hybrids was twice as high as that of the CS-rich hybrids. 3) Enzymatic degradation of the hybrid CS-DS subfractions by chondroitin AC and ABC lyases revealed that the specific radioactivity of the CS and DS disaccharide units released from the DS-rich hybrids was twice as high as those isolated from the CS-rich hybrids, but within each hybrid fraction the galactosamine moieties of the CS and DS units and their glucuronic and iduronic acid components exhibited equal specific radioactivities. 4) The results strongly support the assumption that distinct compartments exist for the formation of hybrid CS-DS proteoglycans with different proportions of CS and DS.

Animals↗
PubMedDate not supplied

Plasma norepinephrine variations with dietary sodium intake.

Plasma catecholamine and renin activity levels were measured across a range of dietary sodium intakes (10--300 mEq/day) in 20 normal male volunteers. Supine plasma norepinephrine levels presented a triphasic pattern in relation to urine sodium, whereas epinephrine levels were not significantly altered by sodium intake, and renin showed the well-known hyperbolic relationship to urine sodium excretion. Highest supine norepinephrine values occurred at low salt intakes, the lowest when sodium excretion was between 100 and 180 mEq/day, and intermediate when sodium excretion was greater than 180 mEq/day. These findings show that sodium intake is an important consideration in the interpretation of plasma norepinephrine levels.

Adult↗
PubMedDate not supplied

Decreased Beta-adrenoreceptor responsiveness as related to age, blood pressure, and plasma catecholamines in patients with essential hypertension.

The role of the sympathetic nervous system as it relates to adrenoreceptor-mediated hemodynamic responses was investigated in patients with essential hypertension and in normal subjects of similar age. An age-related increase in plasma norepinephrine (PNE) concentrations observed in 36 recumbent normal subjects (r = 0.623, p less than 0.001) was not found in 56 patients; the latter included some young patients with high values. Sympathetic overactivity in patients (n = 24) as compared with normotensive subjects (n = 20) was suggested by a greater increase in PNE upon standing (242 +/- 34 vs 155 +/- 25 pg/ml (SEM), p less than 0.05) and persistently higher plasma epinephrine (PE) concentrations at rest and during equieffective exercise (p less than 0.05). In patients, PNE was directly related to systolic (r = 0.57, p less than 0.01) and diastolic (r = 0.53, p less than 0.01) blood pressure. Older age was associated with diminished exercise tachycardia and increased blood pressure responses to exercise, which were both more pronounced in hypertensive patients. This higher pressure/lower heart rate pattern was paralleled by an age-related decrease in isoproterenol sensitivity in normal subjects (0.97 +/- 0.15 in six below age 34 years, 1.31 +/- 0.30 in eight between 35--49 years, and 1.82 +/- 0.12 microgra/m2 in six above 50 years), which was also more pronounced (p less than 0.05) in hypertensive patients (1.20 +/- 1.18 in seven below age 34 years, 2.42 +/- 0.30 in nine between 35--49 years, and 6.73 +/- 2.44 micrograms/m2 in eight above 50 years). Thus, an increase in the patients' blood pressure and age is associated with a progressive reduction in beta-adrenoreceptor sensitivity and/or reactivity. Defective beta-adrenoreceptor-mediated responses may result in unopposed alpha-adrenoreceptor-mediated vasoconstriction and thereby contribute to the development of hypertension.

Adult↗
PubMedDate not supplied

Enhanced alpha-adrenoreceptor-mediated vasoconstriction in essential hypertension.

Forearm blood flow (FAF) has been determined using venous occlusion plethysmography in 24 patients with essential hypertension (EHT) and in 16 age-matched normotensive subjects (NT) under basal resting conditions, following nonspecific vasodilatation with sodium nitroprusside and after intraarterial infusion of the postjunctional alpha-blocking drug, prazosin. Under basal conditions, FAF was significantly higher in EHT than in NT. Infusion of sodium nitroprusside produced a similar absolute increase in FAF in both groups, whereas postjunctional alpha-blockade with prazosin led to a significantly greater increase in FAF in EHT than in NT. A positive correlation was found between plasma epinephrine concentration and prazosin-induced FAF in EHT but not in NT. These results suggest an enhanced postjunctional alpha-adrenoreceptor-mediated vasoconstrictor component in established EHT.

Adult↗
PubMedDate not supplied

Factors influencing the hypotensive effects of calcium antagonists.

The antihypertensive efficacy of monotherapy with the calcium antagonists nifedipine (n = 60) and verapamil (n = 43) was investigated in patients with essential hypertension. Relationships between age, pretreatment blood pressure, pretreatment plasma renin activity, and hypotensive response were examined. Intraindividual differences in the responses to both drugs were also studied (n = 16). Treatment with verapamil had to be discontinued because of constipation in one patient; treatment with nifedipine was discontinued because of headache in 11 and ankle edema in one. The antihypertensive efficacy of nifedipine and verapamil was comparable and was positively related to pretreatment mean blood pressure (p less than 0.001) and inversely to pretreatment plasma renin activity (p less than 0.05). With verapamil, the fall in blood pressure correlated positively with the patient's age (p less than 0.001). Thus, calcium antagonists can be used as first-line drugs, especially in older and low renin patients. The relationship between the antihypertensive response and pretreatment blood pressure suggests that there may be a calcium influx-dependent vasoconstrictor mechanism in essential hypertension which may be more pronounced in patients with low plasma renin.

Administration, Oral↗
PubMedDate not supplied

Endothelial dysfunction in hypertension.

Hypertension is an important risk factor for the development of atherosclerosis and endothelial dysfunction may be a key mechanism. The nitric oxide mediated vasodilator function of the endothelium has been widely studied as a test of endothelial integrity in patients with hypertension and impaired basal and muscarinic agonist stimulated components of nitric oxide mediated vascular tone have been found in coronary, forearm and cutaneous resistance vessels and in coronary and forearm conduit vessels. The underlying abnormalities of these changes are unknown but it is likely to be a secondary phenomenon due to increased blood pressure. However, endothelial dysfunction as assessed by response to muscarinic agonists does not occur in all patients and antihypertensive therapy so far has been mostly unable to reverse it. Although widely used the response to acetylcholine has some shortcomings and it remains to be established what parameter best reflects endothelial dysfunction. The relationship of such abnormalities to the present or future atherosclerosis needs to be defined.

Acetylcholine↗
PubMedDate not supplied

Enhanced vasodilatation in essential hypertension by calcium channel blockade with verapamil.

The dependency of arteriolar tone on calcium influx was studied in 11 patients with essential hypertension (EH) and compared to 11 age-matched normotensive subjects (NT) by measuring the forearm blood flow response to intraarterial infusion of the calcium channel blocker verapamil (Verap) and the non-specific vasodilator sodium nitroprusside (Nip) using venous occlusion plethysmography. Verap in incremental dosages from 1 to 75 micrograms/100 ml forearm tissue induced a greater increase in forearm blood flow ( delta FAF) in EH then in NT, whereas there was no significant difference in delta FAF following Nip 1,2 micrograms/100 ml tissue. Delta FAF to Verap as adjusted for delta FAF to Nip was still greater in EH than in NT. Delta FAF to all dosages of Verap correlated positively with basal plasma epinephrine concentration in EH. At the two highest dosages of Verap, systemic blood pressure fell in EH, and the Verap-induced vasodilator (as adjusted for the response to Nip) correlated negatively to plasma renin activity or plasma angiotensin II concentration. These findings support the concept of an increased dependency of arteriolar tone on calcium influx in EH, which is related to the activity of the sympathetic nervous system. This association may be due to a common underlying derangement in transmembranous ionic fluxes in smooth muscle cells and sympathetic neurons in EH.

Adult↗