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Biomedical subjects

G W Lambert

Publications and source records attributed to G W Lambert.

43 records · Page 3Linked to original sources
PubMed1991

Exercise training lowers resting renal but not cardiac sympathetic activity in humans.

Endurance exercise training has previously been shown to reduce the plasma concentration of norepinephrine. Whether reduction in sympathetic activity is responsible for the blood pressure-lowering effects of exercise training is unknown. Using a radiotracer technique, we measured resting total, cardiac, and renal norepinephrine spillover to plasma in eight habitually sedentary healthy normotensive men (aged 36 +/- 3 years, mean +/- SEM) after 1 month of regular exercise and 1 month of sedentary activity, performed in a randomized order. One month of bicycle exercise 3 times/wk (40 minutes at 60-70% maximum work capacity) reduced resting blood pressure by 8/5 mm Hg (p less than 0.01) and increased maximum oxygen consumption by 15% (p less than 0.05). The fall in blood pressure was attributable to a 12.1% increase in total peripheral conductance. Total norepinephrine spillover to plasma was reduced by 24% from a mean of 438.8 ng/min (p less than 0.05). Renal norepinephrine spillover fell by an average of 41% from 169.4 ng/min with bicycle training (p less than 0.05), accounting for the majority (66%) of the fall in total norepinephrine spillover. Renal vascular conductance was increased by 10% (p less than 0.05), but this constituted only 18% of the increase in total peripheral conductance. There was no change in cardiac norepinephrine spillover. The reduction in resting sympathetic activity with regular endurance exercise is largely confined to the kidney. The magnitude of the fall in renal vascular resistance, however, is insufficient to directly account for the blood pressure-lowering effect of exercise, although other effects of inhibition of the renal sympathetic outflow may be important.

Adult↗
PubMed1990

Altered venous responses to vasoconstrictor agonists and nerve stimulation in human primary hypertension.

The reactivity of human veins, biopsied from the forearms of 15 patients with untreated primary hypertension and 14 normotensive subjects, was studied in vitro. Veins of hypertensive patients were less distensible since the slope of their wall tension-circumference relationships was steeper than in normotensive subjects. There was no difference between the groups with regard to their sensitivity (location of the concentration corresponding to 50% of the maximum response) or their normalized maximum contractile force (Fmax/unit radius) in response to potassium or serotonin. However, veins from hypertensive subjects were less sensitive to noradrenaline and the selective alpha 2-adrenoceptor agonist UK14304, and showed a fall in normalized Fmax with all alpha-adrenoceptor agonists. In contrast, in veins from hypertensive subjects, normalized Fmax was 3.7 times higher in response to angiotensin II than in veins from normotensive subjects. Despite the reduced responses to exogenous alpha-adrenoceptor agonists, contractile responses to transmural field stimulation were enhanced in veins from hypertensive patients. There was no evidence of medial hypertrophy in the veins of hypertensive subjects. The effect of selective alpha 2-adrenoceptor blockade suggested a decrease in prejunctional autoinhibition, while the effect of desipramine on field stimulation and tritiated noradrenaline efflux suggested a decreased neuronal amine uptake in veins of hypertensive subjects. We conclude that veins in hypertension are stiffer, have reduced alpha-adrenoceptor responsiveness, and generate a greater Fmax in response to angiotensin II and nerve stimulation when compared with veins from normotensive subjects.

Adult↗
PubMed1989

Hydrocortisone-induced hypertension in humans: pressor responsiveness and sympathetic function.

Oral hydrocortisone increases blood pressure and enhances pressor responsiveness in normal human subjects. We studied the effects of 1 week of oral hydrocortisone (200 mg/day) on blood pressure, cardiac output, total peripheral resistance, forearm vascular resistance, and norepinephrine spillover to plasma in eight healthy male volunteers. Although diastolic blood pressure remained unchanged, systolic blood pressure increased from 119 to 135 mm Hg (SED +/- 3.4, p less than 0.01), associated with an increased cardiac output (5.85-7.73 l/min, SED +/- 0.46, p less than 0.01). Total peripheral vascular resistance fell from 15.1 to 12.2 mm Hg/l/min (SED +/- 1.03, p less than 0.05). Resting forearm vascular resistance remained unchanged, but the reflex response to the cold pressor test was accentuated, the rise in resistance increasing from 10.5 mm Hg/ml/100 ml/min (R units) before treatment to 32.6 R units after treatment (SED +/- 6.4, p less than 0.025). The rise in forearm vascular resistance accompanying intra-arterial norepinephrine (25, 50, and 100 ng/min) was also significantly greater after hydrocortisone, increasing from an average of 14.9 +/- 2.4 R units before treatment to 35.1 +/- 5.5 R units after hydrocortisone (SED +/- 6.0, p less than 0.05). A shift to the left in the dose-response relation and fall in threshold suggested increased sensitivity to norepinephrine after treatment. Measurement of resting norepinephrine spillover rate to plasma and norepinephrine uptake indicated that overall resting sympathetic nervous system activity was not increased. The rise in resting blood pressure with hydrocortisone is associated with an increased cardiac output (presumably due to increased blood volume).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Release of noradrenaline into the cerebrovascular circulation in patients with primary hypertension.

The conventional view is that a 'blood-brain barrier' prevents the passage into the bloodstream of noradrenaline released as a transmitter in the brain. When we tested directly for noradrenaline spillover, sampling via high right and left internal jugular venous catheters in 22 untreated patients with primary hypertension, release of noradrenaline into the cerebrovascular circulation was detected. The concentration of noradrenaline was 14.8% (mean 0.29 nmol/l) higher in right jugular venous than arterial plasma, and 29.8% (mean 0.55 nmol/l) higher in left (both P less than 0.02, Student's paired t-test). Asymmetry in the cerebral venous drainage pattern (right jugular typically largely represents cortical flow, left jugular subcortical flow) and flow rate (usually lower on the left) may underlie the higher venoarterial plasma concentration gradient on the left. Cerebral noradrenaline overflow was calculated from the cerebral plasma flow, the venoarterial noradrenaline plasma concentration gradient across the brain and transcerebral extraction of radiolabelled noradrenaline. Mean cerebral noradrenaline spillover was 220 pmol/min, accounting for 9.1% of total noradrenaline release to plasma (determined by isotope dilution). Since the ganglionic blocker arfonad reduced whole-body noradrenaline spillover (principally derived from sympathetic nerves), but not cerebral spillover, the noradrenaline overflow appears to originate from brain neurones and not cerebrovascular sympathetic nerves. Jugular venous noradrenaline measurements may provide a direct 'window' into noradrenergic brain mechanisms in primary hypertension, with bilateral sampling perhaps allowing differentiation of cortical from subcortical neurotransmitter function.

Blood-Brain Barrier↗
PubMedDate not supplied

Spontaneous splenic rupture associated with thrombolytic therapy and/or concomitant heparin anticoagulation.

Two cases of spontaneous splenic rupture in connection with thrombolytic therapy and concomitant heparin anticoagulation are reported. One patient was being treated for peripheral arterial graft occlusion using intraarterial urokinase, the other received intravenous infusion of streptokinase for acute myocardial infarction. Neither patient had a condition predisposing to splenic rupture. Although rare, previous reports of spontaneous splenic rupture associated with thrombolytic therapy and/or anticoagulation have been reported. Splenic rupture as a complication of thrombolytic therapy and/or anticoagulation should be considered when unexplained abdominal symptoms, hypotension, or blood loss is encountered.

Aged↗
PubMedDate not supplied

Central nervous system noradrenergic control of sympathetic outflow in normotensive and hypertensive humans.

We applied transmitter washout methodology, sampling internal jugular venous plasma via a percutaneously placed catheter, to study CNS norepinephrine release in humans and its relation to peripheral sympathetic activity. Norepinephrine overflows into the venous drainage of the brain, as do its precursor, DOPA, and metabolites DHPG and MHPG, indicating that the blood-brain barrier provides an incomplete impediment to their outward flux from the brain. Pharmacological testing with two drugs which altered CNS norepinephrine turnover, the tricyclic antidepressant desipramine and the ganglionic blocker, trimethaphan, demonstrated a direct relation existed between CNS norepinephrine release and sympathetic nerve firing rates. In essential hypertension, the sympathetic activation commonly present was associated with, and possibly caused by increased CNS release of norepinephrine, manifested in elevated overflow of norepinephrine, MHPG and DHPG from the brain. Bilateral jugular sampling, coupled with a cerebral venous sinus scan to delineate the drainage pattern, demonstrated that this increased norepinephrine release was confined to subcortical forebrain regions.

Blood Pressure↗