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Biomedical subjects

P Smits

Publications and source records attributed to P Smits.

At least 91 records · Page 5Linked to original sources
PubMed1998

Insulin-induced vasodilatation and endothelial function in obesity/insulin resistance. Effects of troglitazone.

Insulin resistance is associated with a decreased vasodilator response to insulin. Because insulin's vasodilator effect is nitric oxide dependent, this impairment may reflect endothelial dysfunction. Troglitazone, an insulin-sensitiser, might thus improve insulin-dependent and/or endothelium-dependent vascular function in insulin resistant obese subjects. For 8 weeks, fifteen obese subjects were treated with either 400 mg troglitazone once daily or placebo, in a randomised, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses (plethysmography) to intra-arterial administered acetylcholine and sodium nitroprusside; insulin sensitivity and insulin-induced vascular and neurohumoral responses (clamp); vasoconstrictor responses to NC-monomethyl-L-arginine (L-NMMA) during hyperinsulinaemia; and ambulatory 24-h blood pressure (ABPM). Baseline data (placebo) of obese subjects were compared with those obtained in lean control subjects. Obese subjects were insulin resistant compared with leans (whole-body glucose uptake: 26.8+/-3.0 vs. 53.9+/-4.3 [tmol kgl min-, p < 0.001). Troglitazone improved whole-body glucose uptake (to 31.9+/-3.3 micromol x kg(-1) x min(-1) , p=0.028), and forearm glucose uptake (from 1.09+/-0.54 to 2.31+/-0.69 micromol dL(-1) x min(-1), p=0.006). Insulin-induced vasodilatation was blunted in obese subjects (percent increase in forearm blood flow (FBF) in lean 66.5+/-23.0%, vs. 10.1+/-11.3% in obese, p=0.04), but did not improve during troglitazone. Vascular responses to acetylcholine, sodium nitroprusside and L-NMMA did not differ between the obese and lean group, nor between both treatment periods in the obese individuals. In conclusion, in insulin resistant obese subjects, endothelial vascular function is normal despite impaired vasodilator responses to insulin. Troglitazone improved insulin sensitivity but it had no effects on endothelium-dependent and -independent vascular responses. These data do not support an association between insulin resistance and endothelial function.

Acetylcholine↗
PubMed1998

The role of 11 beta-hydroxysteroid dehydrogenase in the pathogenesis of hypertension.

The two 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isozymes catalyze the interconversion of cortisol and cortisone. Type 1 11 beta-HSD (11 beta-HSD1) has bidirectional activity, while type 2 11 beta-HSD (11 beta-HSD2) mainly converts cortisol into cortisone. Of these two hormones only cortisol has affinity to mineralocorticoid receptors (MRs) and thus induces mineralocorticoid effects. A normal activity of 11 beta-HSD2 is crucial for prevention of mineralocorticoid activity of cortisol. Absent or decreased 11 beta-HSD2 activity results in cortisol-mediated hypermineralocorticoid hypertension. In several hypertensive syndromes a decreased 11 beta-HSD2 activity has been described as the pathogenetic mechanism of the increased blood pressure. In the apparent mineral corticoid excess (AME) syndrome type 1, absence of 11 beta-HSD2 activity is caused by mutations in the gene coding for 11 beta-HSD2. In licorice-induced hypertension glycyrrhetinic acid, the active substituent of licorice, inhibits 11 beta-HSD2 resulting in an acquired hypermineralocorticoid state. 11 beta-HSD2 activity is not decreased in glucocorticoid hypertension (Cushing's syndrome). In essential hypertension some evidence for decreased systemic and skin activity of 11 beta-HSD1 and/or 11 beta-HSD2 has been found, while renal activity of both isozymes appears to be normal. 11 beta-HSD2 activity is also present in cardiovascular myocytes of humans and dogs, and inhibition of 11 beta-HSD potentiates the vascular response to catecholamines. Although MRs in the central nervous system have been incriminated in the pathogenesis of mineralocorticoid hypertension, a pathophysiological role for 11 beta-HSD2 has not yet been described. Finally, in the placenta 11 beta-HSD2 reduces fetal exposure to maternal glucocorticoids and a decreased activity of this isozyme may result in low birth weight and increased risk of high blood pressure at adult age.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Insulin stimulates epinephrine release under euglycemic conditions in humans.

In healthy subjects, acute physiological hyperinsulinemia induces activation of the sympathetic nervous system, but in the absence of hypoglycemia, plasma epinephrine levels have not been found to increase during insulin administration. However, the venous level of epinephrine reflects the net result of release, clearance, and uptake and therefore is not a good measure of adrenomedullary epinephrine secretion. The influence of 90 minutes of euglycemic physiological hyperinsulinemia (60 mU x m(-2) x min(-1); plasma insulin concentration, approximately 700 pmol x L[-1]) on epinephrine kinetics using the 3H-epinephrine tracer method was studied in 12 healthy normotensive, non-obese subjects. After bolus injection, [3H]-epinephrine was continuously infused with arterial and venous blood sampling at regular intervals, enabling calculation of total body (systemic) and forearm epinephrine release and clearance. Studies were performed in the basal state and during sympathetic stimulation by lower-body negative pressure (LBNP) of -15 mm Hg for 15 minutes. Control experiments ("sham" clamps, but with LBNP) were performed in four of the 12 individuals. Euglycemic hyperinsulinemia (all arterial glucose samples > or = 4.2 mmol x L[-1]) induced an increase of the arterial epinephrine concentration (P = .03), and tended to increase total body epinephrine release (P = .08). Total body epinephrine clearance did not change during hyperinsulinemia. The insulin-induced increase in forearm blood flow ([FBF] by plethysmography, from 3.0 +/- 0.4 to 3.8 +/- 0.6 mL x dL(-1) x min(-1), P = .01) was strongly correlated with the increase in arterial epinephrine (r = .78, P < .01). Plasma epinephrine concentrations did not change during control experiments (sham clamp). Sympathetic stimulation alone as induced by LBNP did not stimulate epinephrine release. However, the combination of insulin and LBNP significantly increased epinephrine release (from 0.37 +/- 0.06 to 0.56 +/- 0.12 nmol x m(-2) x min(-1), P = .03). We conclude that acute physiological hyperinsulinemia under euglycemic conditions induces epinephrine release. This effect is enhanced when hyperinsulinemia is combined with sympathetic stimulation by LBNP. Due to increased forearm removal, venous epinephrine concentrations hardly change. Epinephrine release was strongly correlated with the hemodynamic effects of insulin.

Adult↗
PubMed1998

Influence of the arm position on intra-arterial blood pressure measurement.

The reference level for the measurement of blood pressure (BP) is the level of the right atrium. In practice this is regularly disregarded, as the patient's arm is usually placed lower than the right atrial level. The aim of the study was to determine the influence of first, different arm positions and second, different transducer positions on the intra-arterially (i.a.) recorded BP. In 16 healthy men (age 28.1 +/- 8.0 (s.d.) years), i.a. BP was recorded at the left arm in supine position, using a 5-7 cm long cannula. The baseline position was with the tip of the cannula placed precisely at the level of the right atrium. Subsequently, the following changes were made: 5, 10, 15 and 20 cm above and 5, 10, 15, and 20 cm below the baseline position. A 2-min rest period was allowed in each position before the BP was measured. The whole procedure was done either with the transducer connected to the arm at the place of the cannula (n = 7), or with the transducer placed next to the subject and continuously kept at the right atrial level during the BP measurement (n = 9). Simultaneously, baseline BP was measured indirectly, with a standard mercury sphygmomanometer, in the opposite arm maintained with the cubital fossa at the right atrial level during the whole procedure. This resulted in the first group of seven volunteers for both the i.a. systolic (SBP) and diastolic BP (DBP) values to significantly decrease (P < 0.001) when the arm together with the transducer were elevated above the level of the right atrium, and returned to the initial value when the arm and the transducer were placed back at the right atrial level. Intra-arterial SBP and DBP significantly (P < 0.001) increased as the arm, together with the transducer, were lowered below the right atrial level and returned to the initial value when the arm and the transducer were placed back at the right atrial level. In both directions, each 5 cm change in the arm level was accompanied by a 3-4 mm Hg change in the i.a. BP value. The baseline BP, measured sphygmomanometrically at the contralateral arm, remained constant during the whole duration of the procedure. The changes in the i.a. BP were minimal in the second group of nine subjects in which only the arm but not the transducer was placed at different levels. We conclude that small deviations in arm position above or below the 'gold standard', ie, the fossa cubiti at the right atrial level, will result in largely erroneous BP values. The correct positioning of the arm during BP measurement is therefore mandatory for the diagnosis and follow-up of hypertensive subjects.

Adult↗
PubMed1998

Influence of angiotensin converting enzyme inhibition and angiotensin II type 1 receptor antagonism on renal sodium and water handling and albuminuria during infusion of atrial natriuretic factor into healthy volunteers.

BACKGROUND: Atrial natriuretic factor increases urinary sodium and water excretion. It also causes an increase in albuminuria. Angiotensin converting enzyme inhibition attenuates the effects of atrial natriuretic factor on renal sodium and water handling; however, it is not known whether this effect is mediated by the accompanied decrease in blood pressure or by suppression of the renin-angiotensin system. OBJECTIVE: To test the hypothesis that atrial natriuretic factor mediates natriuresis and diuresis by inhibiting angiotensin II, by studying the effects of the angiotensin converting enzyme inhibitor enalapril and the angiotensin II type 1 receptor antagonist losartan. In addition, the effects of these drugs on atrial natriuretic factor-induced albuminuria were examined. DESIGN AND METHODS: We investigated the effects of enalapril and losartan on atrial natriuretic factor-induced changes in urinary excretion of sodium, water and albumin from eight healthy volunteers. Measurements of systemic and renal haemodynamics in these subjects were performed before and during a 2 h infusion of atrial natriuretic factor [0.01 microg/kg per min (low dose) for the first 60 min and 0.02 microg/kg per min (high dose) for the second 60 min]. Measurements were performed after 5 days of pretreatment with placebo, 50 mg losartan or 20 mg enalapril daily. RESULTS: Mean arterial pressures during the clearance study were 84.6 +/- 1.7 mmHg after placebo, 84.0 +/- 2.2 mmHg after losartan treatment and 80.0 +/- 2.5 mmHg after enalapril treatment (P < 0.05). Plasma renin activity was significantly increased both by losartan and by enalapril treatments. Neither enalapril nor losartan treatment attenuated atrial natriuretic factor-induced changes in renal haemodynamics. After placebo pretreatment, fractional urinary excretion of sodium increased significantly during infusion of atrial natriuretic factor. Losartan treatment did not influence the increase in urinary excretion of sodium during infusion of atrial natriuretic factor, whereas enalapril treatment significantly attenuated this increase (P < 0.01). Atrial natriuretic factor significantly increased albuminuria. Neither losartan nor enalapril treatment reduced atrial natriuretic factor-induced albuminuria. CONCLUSIONS: Enalapril treatment lowered blood pressure and attenuated the atrial natriuretic factor-induced increase in urinary excretion of sodium. In contrast, the angiotensin II type 1 receptor antagonist losartan, at a dosage that did not lower blood pressure, did not attenuate the increase in urinary excretion of sodium. These data indicate that atrial natriuretic factor increases natriuresis and diuresis independently of angiotensin II. The increase in albuminuria during infusion of atrial natriuretic factor was not influenced by enalapril and losartan treatments.

Adult↗
PubMed1998

Does it matter whether blood pressure measurements are taken with subjects sitting or supine?

BACKGROUND: Several guidelines for the management of hypertension do not give special preference to a specific position of the patient during blood pressure measurement, suggesting that blood pressure readings taken with patients sitting and with patients supine are interchangeable. OBJECTIVE: To test whether there is any difference between the blood pressure readings with patients sitting and supine. DESIGN AND METHODS: Blood pressure and heart rate were measured three times each for 245 subjects (171 hypertensives), with subjects both sitting and supine, simultaneously on both arms, with a Hawksley random-zero sphygmomanometer on the right arm and a semi-automatic oscillometric device (Bosomat) on the left arm. The sequence of the two positions was randomized. The procedure was repeated on a second occasion for 49 subjects (41 hypertensives) with the sequence of the positions reversed. Because there was no systematic difference among the three readings per position, the averages of the three blood pressure and heart rate readings with subjects sitting and supine were compared and the influences of age, body mass index, hypertension and medication on the difference were examined. RESULTS: We found no influence of the subject's body posture on the systolic blood pressure. We found a higher diastolic blood pressure [by 5.2+/-0.4 mmHg (mean+/-SEM), P< 0.001 with Hawksley random-zero sphygmomanometer] and a greater heart rate [by 1.5+/-0.3 beats/min (mean+/-SEM), P< 0.001] with subjects sitting. The sitting minus supine differences for diastolic blood pressure and heart rate decreased significantly with increasing age (P< 0.001). We found no effect of body mass index, hypertension and medication on the sitting - supine differences. CONCLUSIONS: The subject's body posture influenced especially the diastolic blood pressure and heart rate, both of them being significantly higher with patients sitting rather than supine. This effect decreased with age. Thus, for indirect blood pressure measurement, diastolic blood pressure values obtained with subjects sitting and supine cannot automatically be regarded as equivalent.

Adult↗
PubMed1998

Haemodynamic actions of insulin.

Several lines of evidence indicate a significant association between insulin and cardiovascular disease. This association might be explained by direct (cardio) vascular effects of insulin. Two hemodynamic actions of insulin are discussed in this review; it induces direct vasodilation in skeletal muscle and stimulation of the sympathetic nervous system. These closely linked effects normally offset each other. Although more insight has been obtained into responses in insulin-resistant individuals and possible mechanisms, direct evidence to support a causative role for insulin is not yet available.

Animals↗
PubMed1998

Thiazide-induced vasodilation in humans is mediated by potassium channel activation.

-Hydrochlorothiazide and indapamide are thought to exert their hypotensive efficacy through a combined vasodilator and diuretic effect, but in vivo evidence for a direct vascular effect is lacking. The presence and mechanism of a direct vascular action of hydrochlorothiazide in vivo in humans were examined and compared with those of the thiazide-like drug indapamide. Forearm vasodilator responses to infusion of placebo and increasing doses of hydrochlorothiazide (8, 25, and 75 microg. min-1. dL-1) into the brachial artery were recorded by venous occlusion plethysmography. Dose-response curves were repeated after local tetraethylammonium (TEA) administration to determine the role of potassium channel activation and, in patients with the Gitelman syndrome, to determine the role of the thiazide-sensitive Na-Cl cotransporter in the vasodilator effect of hydrochlorothiazide. Vascular effects of hydrochlorothiazide were compared with those of indapamide in both normotensive (mean arterial pressure, 85+/-7 mm Hg) and hypertensive (mean arterial pressure, 124+/-16 mm Hg) subjects. At the highest infusion rate, local plasma concentrations of hydrochlorothiazide averaged 11.0+/-1.6 microg/mL, and those of indapamide averaged 7. 2+/-1.5 microg/mL. In contrast to indapamide, hydrochlorothiazide showed a direct vascular effect (maximal vasodilation, 55+/-14%; P=0. 013), which was inhibited by TEA (maximal vasodilation after TEA, 13+/-10%; P=0.02). The response was not dependent on blood pressure and was similar in patients with Gitelman syndrome, indicating that absence of the Na-Cl cotransporter does not alter the vasodilatory effect of hydrochlorothiazide. The vasodilator effect of hydrochlorothiazide in the human forearm is small and only occurs at high concentrations. The mechanism of action is not mediated by inhibition of vascular Na-Cl cotransport but involves vascular potassium channel activation. In contrast, indapamide does not exert any direct vasoactivity in the forearm vascular bed.

Antihypertensive Agents↗
PubMed1998

Combination diuretic therapy in severe congestive heart failure.

Severe congestive heart failure (CHF) is often characterised by fluid retention. A (chronic) state of overhydration has a negative influence on both the quality of life and prognosis of these patients. Therefore, the use of diuretics remains a cornerstone in the treatment of heart failure. However, diuretic resistance, a failure to correct the hydration state adequately with the use of conventional dosages of loop diuretics, is a frequently occurring complication in the treatment of advanced stages of CHF. Several intra- and extrarenal mechanisms may be involved in the development of diuretic resistance. An important pathophysiological mechanism leading to diuretic resistance seen after chronic use of loop diuretics is the functional adaptation of the distal tubule. Studies in animals demonstrate that the sodium reabsorption capacity of this nephron segment increases significantly when the sodium delivery to this segment is augmented, as is the case during administration of loop diuretics. The use of combinations of diuretics acting on different segments of the nephron appears to be an effective option in the treatment of diuretic resistance. Several combinations have been used; however, the combination of a loop diuretic and a thiazide drug acting on the distal tubule appears to be the most effective. However, since the use of this combination may lead to serious adverse effects such as hypokalaemia, metabolic alkalosis and dehydration, careful monitoring of the patient of combination diuretic therapy is necessary.

Diuretics↗
PubMed1998

Troglitazone decreases the proportion of small, dense LDL and increases the resistance of LDL to oxidation in obese subjects.

OBJECTIVE: Insulin resistance is associated with a predominance of small, atherogenic LDL particles that are more prone to oxidative modification. Treatment with the insulin-sensitizer troglitazone may improve LDL composition and resistance to oxidation. RESEARCH DESIGN AND METHODS: In a randomized double-blind crossover design, 15 obese subjects were treated with either 400 mg troglitazone daily or placebo for 8 weeks. Insulin sensitivity (clamp), (apo)lipoproteins, LDL subclass pattern, plasma TBARS, and ex vivo LDL oxidation were determined. RESULTS: Troglitazone treatment improved insulin sensitivity. LDL cholesterol increased from 2.58 +/- 0.18 to 2.77 +/- 0.20 mmol/l (P = 0.03) because of an increase in large (buoyant) LDL1 (from 0.45 +/- 0.04 to 0.62 +/- 0.09 mmol/l, P = 0.008). Because small (dense) LDL3 decreased, LDL1:LDL3 ratio increased (P = 0.02). Plasma TBARS concentration declined significantly, and the lag time of ex vivo LDL oxidation showed a small but significant increase. CONCLUSIONS: In obese subjects, treatment with troglitazone improves insulin sensitivity, increases the ratio of large buoyant to small dense LDL, and appears to enhance the resistance of the LDL particle to oxidation. These qualitative changes in lipoproteins may have a beneficial effect on cardiovascular risk profile and compensate for a small increase in LDL cholesterol.

Adult↗
PubMed1998

Adenosine-induced renal vasodilatation is prolonged in renal artery stenosis.

OBJECTIVE: The objective of this study was to determine whether the response of renal blood flow (RBF) to adenosine infusions differs between hypertensive patients with and without renal artery stenosis (RAS). DESIGN AND METHODS: Twenty-one hypertensive patients who underwent diagnostic angiography of the renal arteries were studied. Nine patients (median age 51 years; 45-61 interquartile ranges) were diagnosed as having essential hypertension (EH). Twelve patients (median age 52 years; 50-58) had hypertension and renal artery stenosis. In all patients three stepwise increasing doses of adenosine (1, 3 and 10 (microg/kg/min) were infused into the renal artery. RBF was measured before and during infusions by means of the 133xenon wash-out method. Arterial and venous plasma samples for renin concentration were obtained from the renal artery and renal vein. Intraarterial blood pressure and heart rate were monitored continuously. RESULTS: Both groups were similar with respect to age, body mass index, mean arterial pressure and baseline RBF (EH: median 428; RAS 343 ml/min/100 g). Both groups showed a similar dose-related increase in RBF during adenosine infusions (normal kidneys: 9, 21 and 34% change vs baseline; stenotic kidneys: 16, 39 and 52% change vs baseline). Ten minutes after discontinuation of the adenosine infusion, RBF returned to baseline in the normal kidney group, but increased further in the stenotic kidney group (71% vs baseline; P = 0.033). Adenosine infusion did not affect the renin secretion in either group. CONCLUSION: Both essential hypertensive patients and patients with renal artery stenosis show a dose-dependent vasodilatation following adenosine infusion. This vasodilatation is sustained after discontinuation of the adenosine infusion in patients with renal artery stenosis, suggesting a potentiated mechanism for vasodilatation induced by adenosine.

Adenosine↗
PubMed1997

The human extracellular matrix gene 1 (ECM1): genomic structure, cDNA cloning, expression pattern, and chromosomal localization.

The Ecm1 gene encodes an 85-kDa protein of unknown function that was originally identified as a secretory protein of the murine osteogenic stromal cell line MN7. This paper describes the isolation of a genomic clone containing the human ECM1 gene from a chromosome 1 cosmid library and the characterization of its exon-intron structure. The protein coding region comprises 10 exons. The ECM1 gene maps at chromosome 1q21 outside the epidermal differentiation complex region. The ECM1 gene appears to be expressed as a 1.8-kb transcript predominantly in placenta and heart, while an additional 1.4-kb alternatively spliced message was detected in tonsils. The full-length human ECM1 transcript contains 1838 bp and has an overall homology of 79.6% with the mouse Ecm1 cDNA. This transcript codes for a protein of 540 amino acids that is 69.4% identical and 81.3% similar to the corresponding mouse protein. The alternatively spliced variant, 1450 bp long, encodes a protein of 415 amino acids.

Alternative Splicing↗
PubMed1997

Direct vascular effects of furosemide in humans.

BACKGROUND: In humans, hemodynamic changes observed within minutes after systemic administration of furosemide are often referred to as direct vasoactivity. However, these immediate changes do not per se imply a direct vascular effect. We examined the genuine direct vascular effects of furosemide on the human forearm vascular bed and dorsal hand vein. METHODS AND RESULTS: Forearm blood flow in response to infusion of increasing dosages of furosemide into the brachial artery was recorded by venous occlusion plethysmography. Local plasma concentrations of furosemide reached a maximum of 234+/-40 microg/mL during the highest infused dose but did not significantly affect the ratio of flow in the infused/noninfused arms. Venous distensibility of a dorsal hand vein was measured with a linear variable differential transformer. During precontraction with norepinephrine, five increasing dosages of furosemide (1 to 100 microg/min) were administered locally. Additional experiments using local administration of indomethacin or N(G)-monomethyl-L-arginine (L-NMMA) were carried out to determine whether effects were dependent on local prostaglandin or nitric oxide synthesis, respectively. Also, the effects of systemic administration of furosemide were examined. Local administration of furosemide led to a dose-dependent venorelaxation of 18+/-6% at the first to 72+/-16% at the last dose. Indomethacin almost completely abolished furosemide-induced venorelaxation, whereas L-NMMA had no effect. Systemic administration of furosemide resulted in a time-dependent increase of hand vein distensibility, reaching 45+/-11% after 8 minutes. CONCLUSIONS: Furosemide does not exert any direct arterial vasoactivity in the human forearm, even at supratherapeutic concentrations. In contrast, at concentrations estimated to be in the therapeutic range, we observed a dose-dependent direct venodilator effect on the dorsal hand vein that appears to be mediated by local vascular prostaglandin synthesis.

Adult↗
PubMed1997

[Failing diuretics in severe chronic heart failure].

Three patients with chronic heart failure, men aged 29, 78 and 69 years, developed severe dyspnoea and oedema in spite of reduced sodium and fluid intake and medication including furosemide. Heart failure may become 'resistant to diuretics' due to pharmacokinetic and pharmacodynamic causes. High-dose continuous intravenous administration of a loop diuretic may afford relief in such cases, if necessary in combination with a thiazide derivative, an ACE inhibitor, an inotropic agent or an extracorporal technique. Monitoring and correction of the state of hydration of a patient with chronic heart failure may improve the prognosis and the quality of life.

Adult↗
PubMed1997

Cardiovascular pharmacology of purines.

1. This review focuses on the extracellular actions of ATP and adenosine, and in particular their role in cardiovascular regulation. 2. ATP serves as a co-transmitter within the sympathetic nervous system, and is also released from endothelium and aggregating thrombocytes. ATP acts on P2x purinoceptors on vascular smooth muscle cells to induce vasoconstriction. Stimulation of P2y purinoceptors on endothelial cells releases endothelium-derived relaxing factors and causes vasodilatation. This dual action of ATP may have pathophysiological importance by inducing vasospasm at sites of impaired endothelial function and thrombus formation. 3. Adenosine is generated by enzymic degradation of ATP. Its formation is enhanced during ischaemia. Adenosine inhibits noradrenaline release from sympathetic nerve endings, causes vasodilatation via endothelium-dependent and endothelium-independent actions, has important anti-arrhythmic properties and prevents deleterious sequelae of ischaemia. In humans, adenosine evokes a sympatho-excitatory reflex mediated by chemically sensitive receptors and afferent nerves in the kidney, heart and forearm. This reflex may be active during exercise and ischaemia and, because of its potential adverse consequences, it should be considered when developing new therapies to potentiate the anti-ischaemic actions of endogenous adenosine in humans. Adenosine appears to mediate ischaemia-induced pain; a reduced sensitivity to adenosine may underlie silent ischaemia. 4. New drugs that interact with adenosine formation or degradation or with adenosine receptors are under development. These have potential therapeutic application in the treatment of ischaemia and other circulatory disorders.

Adenosine↗