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Biomedical subjects

G A FitzGerald

Publications and source records attributed to G A FitzGerald.

228 records · Page 13Linked to original sources
PubMed1980

The renin--kallikrein--prostaglandin system: plasma active and inactive renin and urinary kallikrein during prostacyclin infusion in man.

Renal prostaglandins are integrated with the kallikrein-kinin and renin-angiotension systems in a vasoactive hormone complex. Prostacyclin potently stimulates renin release from rabbit cortical slices and plasma renin activity rises in response to prostacyclin infusion in man. Prostaglandins also stimulate the production of kallikrein, a potential activator of renin in vivo. To investigate the mechanism of prostacyclin induced renin release, human volunteers were infused with prostacyclin 8ngKg-1min-1 and vehicle alone in random order. Despite a marked increase in plasma active renin during prostacyclin both plasma inactive renin and urinary kallikrein failed to alter from control values. Urinary sodium and volume were increased by prostacyclin. The stimulation of renin by intravenous prostacyclin is not mediated by activation of the kallikrein system.

Adult↗
PubMed1979

Interindividual variation in kinetics of infused epinephrine.

1-Norepinephrine was infused continuously for 10 hr into 5 normotensive, male laboratory subjects (mean age, 32.4 +/- 1.9 yr) at a mean rate of 0.06 microgram/kg/min. Mean plasma norepinephrine (NE) rose from the preinfusion level of 0.19 +/- 0.02 microgram/l to a steady state level of 1.22 +/- 0.29 microgram/l. The mean increase in blood pressure was 21.8 +/- 0.9 mm Hg systolic and 14.1 +/- 1.0 mm Hg diastolic. The mean depression in heart rate was 12.7 +/- 1.7 beats/min. The clearance of norepinephrine ranged from 27.9 to 100.0 ml/kg/min (mean. 58.0 +/- 13.8) and was little influenced by acute hemodynamic changes. The volume of distribution ranged widely (0.09 to 0.40 l/kg), the mean value being 13.51 1. The mean norepinephrine half-life was brief, ranging from 1.45 to 2.9 min (mean, 2.09 +/- 0.34 min). There was no evidence of a slowly accumulating high-capacity low-affinity pool of norepinephrine. These results support the use of plasma norepinephrine as an index of sympathetic activity within an individual but not its validity in interindividual comparisons.

Adult↗
PubMed1979

Prostacyclin stimulates the renin angiotensin aldosterone system in man.

The effect of prostacyclin (PGI2) on the renin-angiotensin-aldosterone system (RAA) has been examined in 6 normal male volunteers infused with 3 incremental doses of PGI2. Diastolic blood pressure fell significantly during the infusion of the highest dose of 8 ng/kg/min. Plasma renin activity (PRA) and plasma angiotensin II (AII) increased to 271% and 342% respectively from baseline values. Plasma cortisol (PC), plasma noradrenaline (PNA) and plasma adrenaline (PAD) did not change significantly. Plasma aldosterone (PA) increased slightly 15 minutes after stopping the infusion. These results suggest aht PGI2 stimulates the release of renin in man.

Adult↗
PubMedDate not supplied

Increased formation of distinct F2 isoprostanes in hypercholesterolemia.

BACKGROUND: F2 isoprostanes are stable, free radical-catalyzed products of arachidonic acid that reflect lipid peroxidation in vivo. METHODS AND RESULTS: Specific assays were developed by use of mass spectrometry for the F2 isoprostanes iPF2alpha-III and iPF2alpha-VI and arachidonic acid (AA). Urinary excretion of the 2 F2 isoprostanes was significantly increased in hypercholesterolemic patients, whereas substrate AA in urine did not differ between the groups. iPF2alpha-III (pmol/mmol creatinine) was elevated (P<0.0005) in homozygous familial hypercholesterolemic (HFH) patients (85+/-5. 5; n=38) compared with age- and sex-matched normocholesterolemic control subjects (58+/-4.2; n=38), as were levels of iPF2alpha-VI (281+/-22 versus 175+/-13; P<0.0005). Serum cholesterol correlated with urinary iPF2alpha-III (r=0.41; P<0.02) and iPF2alpha-VI (r=0. 39; P<0.03) in HFH patients. Urinary excretion of iPF2alpha-III (81+/-10 versus 59+/-4; P<0.05) and iPF2alpha-VI (195+/-18 versus 149+/-20; P<0.05) was also increased in moderately hypercholesterolemic subjects (n=24) compared with their controls. Urinary excretion of iPF2alpha-III and iPF2alpha-VI was correlated (r=0.57; P<0.0001; n=106). LDL iPF2alpha-III levels (ng/mg arachidonate) were elevated (P<0.01) in HFH patients (0.32+/-0.08) compared with controls (0.09+/-0.02). The concentrations of iPF2-III in LDL and urine were significantly correlated (r=0.42; P<0.05) in HFH patients. CONCLUSIONS: Asymptomatic patients with moderate and severe hypercholesterolemia have evidence of oxidant stress in vivo.

Adolescent↗
PubMedDate not supplied

Influence of hospitalization and placebo therapy on blood pressure and sympathetic function in essential hypertension.

The decline in blood pressure (BP) in essential hypertensives following hospitalization may result from: 1) regression toward the mean; 2) reduction of anxiety as patients habituate to a new environment; 3) the placebo effect of medication; and 4) an independent effect of hospitalization itself. A randomized crossover study of 12 essential hypertensives demonstrated a fall in supine blood pressure from 165.0/97.9 +/- 2.3/1.1 mm Hg to 154.3/89.6 +/- 2.7/1.1 mm Hg (p less than 0.005) due to hospitalization. A similar reduction in BP from 164.9/99.5 +/- 8.4/4.1 mm Hg to 151.9/93.4 +/- 4.5/1.9 mm Hg (p less than 0.005) resulted from regression toward the mean and habituation during the study period. Urinary catecholamines fell from 68.7 +/- 5.0 to 55.1 +/- 4.3 micrograms/g creatinine/24 hours (p less than 0.05) due to hospitalization and from 56.1 +/- 5.4 to 49.7 +/- 4.3 micrograms/g creatinine/24 hours (p less than 0.05) with time. Although placebo therapy tended to reduce BP, it failed to do so significantly. When expressed as a percentage of the individual's overall mean, urinary catecholamine excretion fell from 110.5% +/- 3.7% to 89.5% +/- 3.7% (p less than 0.001) during hospitalization and from 105.8% +/- 3.9% to 94.2% +/- 3.9% (p less than 0.05) during the outpatient period. Blood pressure and sympathetic activity rapidly returned to prehospitalization values on discharge. These factors may confound the analysis of drug effects on BP and sympathetic activity in essential hypertensives following admission to hospital.

Adult↗
PubMedDate not supplied

COX-2 inhibitors and the cardiovascular system.

Cyclooxygenase-2 selective inhibitors (coxibs) represent a new class of non steroidal anti-inflammatory drugs that exhibit preference for inhibition of cyclooxygenase-2 (COX-2), the COX isoform thought to account largely for prostanoid formation in inflammation. We review the divergent incidence of cardiovascular events derived from the two large clinical trials of coxibs, the Vioxx Gastrointestinal Outcomes Research Trial (VIGOR) and the Celecoxib Long-term Arthritis Safety Study (CLASS), in the context of current understanding of relevant clinical and basic pharmacology. The incidence of cardiovascular events was higher in patients receiving rofecoxib than in those receiving naproxen in VIGOR and did not differ between the groups in CLASS. By contrast, while the primary gastrointestinal (GI) endpoint comparison favored rofecoxib in VIGOR, no significant difference in the incidence of the primary GI endpoint was evident between celecoxib and two NSAID comparators not attained in CLASS. The cardiovascular results in VIGOR may have resulted from chance, a cardioprotective effect of naproxen, or suppression of prostacyclin but not thromboxane on rofecoxib. Differences in cardiovascular outcome between the two trials may also have resulted either from chance, or from aspects of the trial design (such as the use of aspirin by roughly one-fifth of the participants in CLASS), or from differences in the COX-2 selectivity or other pharmacology of the coxibs. Individuals who warrant low-dose aspirin for cardioprotection may have less likelihood of a GI event if they combine aspirin with rofecoxib, rather than a traditional NSAID. However, evidence addressing directly this hypothesis is currently unavailable. On the other hand, coxib consumption alone does not currently warrant initiation of a cardioprotective regimen, such as low-dose aspirin.

Anti-Inflammatory Agents, Non-Steroidal↗