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Biomedical subjects

A Wennmalm

Publications and source records attributed to A Wennmalm.

At least 145 records · Page 8Linked to original sources
PubMed1980

Cardiac prostaglandin formation in man.

The quantitative relationship between various prostaglandins (PGs) formed in the human heart was studied by constant-rate infusion of 14C-labeled arachidonic acid into the aortic root and simultaneous blood sampling from the coronary sinus in six healthy volunteers. After conventional extraction procedures, the various 14C-PGs formed were separated and quantitied by means of thin-layer chromatography and fractionated liquid scintillation spectrometry. Most of the arachidonic acid infused was metabolized, and well defined peaks of 14C-PG were obtained in the chromatograms. 6-keto-PGF 1 alpha constituted the main PG formed, reflecting a considerable synthesis of prostacyclin in the heart. PGs of the D, E, and F weries were formed in roughly equal amounts. In a 54-year-old subject, 6-keto-PGF 1 alpha constituted a greater proportion of PG than in the other subjects. This may reflect a general effect of aging or it may indicate the presence of ischemic heart disease in this subject.

Adult↗
PubMed1979

Evidence for an extra-renal origin of urinary prostaglandin E2 in healthy men.

In order to verify the validity of the assumption that male urinary Prostaglandin (PG) E2 reflects its renal production, PGE2 and PGF2 alpha concentrations were measured by radioimmunoassay in the renal venous plasma (RVP) and urine (U) of 12 male and 4 female healthy volunteers. While women had a similar PGE2/PFG2 alpha ratio in RVP (0.59 +/- 0.18) and U (0.41 + 0.06), men and a significantly (P less than 0.05) higher ratio in U (1.43 +/- 1.72) as compared to RVP (0.54 +/- 0.16). This was largely due to considerably higher and more variable U-PGE1 concentrations (roughly 6 times higher than female values), despite almost identical RVP levels. The possibility of an increased U excretion of a cross-reacting member of the PG-system, as a cause of such apparently high PGE2-like immunoreactivity (LI), was ruled out by TLC characterization of PGE2-LI with three different anti-PGE1 sera. Thus, male U-PGE2 may variably reflect an extra-renal source, such as contamination with trace amounts of seminal fluid. It is concluded that, unless such a contamination can be monitored and corrected for, measurement of male U-PGE1 should be considered of questionable relevance to renal PG-synthesis.

Chromatography, Thin Layer↗
PubMed1979

Prostaglandins contribute to the vasodilation induced by nicotinic acid.

The significance of endogenously formed prostaglandins in the vasodilation induced by nicotinic acid (NIC) was investigated. The forearm venous plasma level of radioimmunoassayed PGE (R-PGE) and the forearm blood flow (FBF) were measured in 13 healthy male volunteers at rest and during infusion of NIC. Each subject was subsequently re-studied after pretreatment with the PG synthesis inhibitor, naproxen. In the absence of naproxen, NIC infusion resulted in an almost four-fold rise in the release of R-PGE and a 60% increase in FBF. Pretreatment with naproxen did not affect the basal release of R-PGE or the basal FBF but inhibited both the release of R-PGE and the increase in FBF following NIC. The data support the hypothesis that the vasodilating effect of NIC is largely dependent upon an increased vascular formation of PG.

Adult↗
PubMed1979

Prostacyclin-dependent coronary vasodilation in rabbit and guinea pig hearts.

Isolated hearts from rabbits or guinea pigs were perfused according to Langendorff and the coronary flow was recorded continuously. In addition, the rabbit heart transmyocardial effluent's content of platelet anti-aggregatory (prostacyclin-like, PCLA) activity was assayed biologically at regular intervals. Perfusion was performed with a solution gassed with 95% O2 in CO2, switching at intervals to a solution gassed with 12% O2 and 5% CO2 in N2. Perfusion with a hypoxic solution elicited reproducible increased in coronary flow. After pretreatment with indomethacin (5 x 10-5M), this increase was completely abolished and in several cases it was reversed to a marked reduction in cornonary flow. The transmyocardial effluent contained, during perfusion with normoxic solution, no detectable or only negligible amounts of PCLA. During hypoxia the efflux of PCAL into the transmyocardial effluent increased markedly. This increase was completely abolished when indomethacin (5 x 10-5M) was added to the solution perfusing the heart. The results strongly suggest that increased coronary vascular formation of prostacyclin plays a key role in the coronary vasodilation induced by hypoxia in rabbit and guinea pig hearts.

Adenosine Diphosphate↗
PubMed1979

Human forearm and kidney conversion of arachidonic acid to prostaglandins.

The capacity of the human forearm and kidney to synthetize different prostaglandins (PGs) was studied, together with the quantitative relationship between the various PGs formed in these organs. 14C-labelled arachidonic acid (14C-AA) was infused in healthy male volunteers at a constant rate into the brachial or the renal artery, with simultaneous sampling of regional venous blood. The venous plasma content of 14C-PGs was extracted, separated with thin-layer chromatography (TLC) and quantified using fractionated liquid scintillation spectrometry. Most of the 14C-AA infused was metabolized and radiopeaks parallel to unlabelled standards of PGD2, PGE2, PGF2 alpha, 6-keto-PGF1 alpha and 13,14-dihydro-15-keto-PGE2 (Me) were obtained. The chromatograms of both the forearm and the kidney plasma contained all the peaks described, but the relative distribution of the 14C-PGs differed between the two tissues. In the cubital venous plasma, the main PG (apart from Me) was 6-keto-PGF1 alpha, indicating a considerable synthesis of PGI2 in the forearm. In the renal venous plasma, on the other hand, PGD2 accounted for the largest part of the authentic 14C-PGs found. Besides the tissue differences, large inter-individual variations were observed. The results demonstrate the existence of both a considerable tissue specificity and an appreciable inter-individual variation in the local conversion of AA to PGs in man.

Adult↗
PubMed1979

A study on the role of endogenous prostaglandins in the development of exercise-induced and post-occlusive hyperemia in human limbs.

The contribution of endogenous PGs to the development of functional (exercise-induced) and reactive (post-occlusive) hyperemia was investigated in healthy volunteers. Leg blood flow during dynamic leg exercise was estimated by an indicator dilution technique. Forearm blood flow during supine leg exercise and forearm and calf blood flow following 5 min of arterial occlusion were measured plethysmographically. All subjects were examined before and after pretreatment with indomethacin, a PG synthesis inhibitor. During leg exercise, and in the absence of indomethacin, a 10-fold rise in leg blood flow was observed. Forearm blood flow increased moderately. Both these blood flow effects of exercise were unaffected by indomethacin. Following arterial occlusion a marked hyperemia developed in the forearm and the calf. Indomethacin significantly reduced the magnitude of the reactive hyperemia both in the forearm and in the calf, decreasing both the peak value and the duration of the vasodilation. These data reveal differences between the mechanisms behind functional and reactive hyperemia in man, suggesting an appreciable contribution of endogenous PGs to post-occlusive vasodilation only.

Adult↗
PubMed1979

Conversion of arachidonic acid to prostaglandins in homogenates of human skeletal muscle and kidney.

The capacity of human skeletal muscle and kidney homogenates to synthetize prostaglandins (PGs) from exogenous precursor was investigated. Low-speed supernatants of muscle as well as renal medullary and cortical homogenates were incubated with 14C-labelled arachidonic acid (14C-AA) prepared as a sodium salt. 14C-PGs in the incubates were extracted, separated with thin-layer chromatography (TLC) and quantified by radioscanning. In the skeletal muscle incubates 14C-AA was converted into 14C-PGs with a time-dependent yield, most effectively after 10--15 min incubation. Well-defined radiopeaks parallel to unlabelled standards of PGD2, PGE2, PGF2 alpha and 6-keto-PGF1 alpha were obtained in the chromatograms. PGE2 was the main PG formed, constituting over 50% of 14C-activity, whereas 6-keto-PGF1 alpha, PGD2 and PGF2 alpha were found in considerably lower proportions. In the renal medullary incubates, PGE2 likewise accounted for the largest part of 14C-PGs formed, but significant relative amounts of PGF2 alpha and PGD2 were also found. A minor peak, corresponding to 6-keto-PGF1 alpha and thus indicating formation of PGI2, was also obtained. In contrast to the medulla, no 14C-PGs could be found in the renal cortical incubates. The results demonstrate the existence of a considerable tissue specificity in the quantitative and qualitative expression of PG biosynthesis in man.

Adult↗
PubMed1979

Cigarette smoking, prostaglandins and reactive hyperemia.

The hypothesis was investigated that cigarette smoking obstructs the blood flow response that develops as a protection against tissue damage in an organ subjected to ischemia (reactive hyperemia). Forearm blood flow was recorded at rest and following forearm ischemia before and after cigarette smoking in healthy male and female volunteers. The experiments were also repeated after pre-treatment of the subjects with indomethacin, a prostaglandin synthesis inhibitor. Before pre-treatment with indomethacin, ischemia induced a reactive hyperemia amounting to 20 +/- 4 ml/100 ml tissue. This hyperemia was significantly (p less than 0.01) reduced by cigarette smoking, to 12 +/- 3 ml/100 ml tissue. After indomethacin, which in itself lowered the reactive hyperemia to 8 +/- 2 ml/100 ml tissue, smoking did not elicit any effect. It is suggested that smoking counteracts reactive hyperemia in tissues by interfering with the same physiological mechanism as indomethacin, i.e. with the vascular formation of PG. The possible significance of this observation in relation to cigarette smoking and ischemic heart disease is stressed.

Adult↗
PubMed1978

Prostaglandin-mediated inhibition of noradrenaline release: V. A comparison of the neuroinhibitory effect of three prostaglandins: E2, I2, and 6-keto-PGF1alpha.

The effect of PGE2, PGI2, and 6-keto-PGF1alpha respectively on the contractile response of the isolated, field-stimulated guinea pig vas deferens was investigated. All three PGs were capable of inhibiting the contractile responses of the vas deferens, but the concentrations required varied considerably: PGE2 was about 700 times more active than PGI2 and about 4600 times more active than 6-keto-PGF1alpha in this respect. It is suggested that PGI2, although formed in tissues with sympathetic innervation, does not play a physiological role as inhibitor of sympathetic transmitter release.

Animals↗
PubMed1978

Effect of exercise on human arterial and regional venous plasma concentrations of prostaglandin E.

Healthy male volunteers underwent catheterization of a brachial artery and subclavian, hepatic, renal, and femoral veins. Blood was sampled simultaneously from all catheters, at rest as well as during supine leg exercise at 130 W. Plasma PGE were extracted and purified, using silicic acid chromatography, and subsequently quantified, using RIA. At rest no release or uptake of PGE was observed in the arm, the splanchnic region, or the leg, but in the kidney an uptake was noted. During exercise a significant release of PGE developed in the arm and in the leg. The data support the hypothesis that vascular PGs play a role in the local adaptation of the circulatory system to exercise.

Adult↗
PubMed1978

Influence of indomethacin on the systemic and pulmonary vascular resistance in man.

1. Indomethacin, an inhibitor of the cyclo-oxygenase system that converts arachidonic acid into prostaglandins and related substances, was infused intravenously in 12 healthy volunteer subjects. 2. Systemic systolic and diastolic blood pressures and heart rate were recorded in all subjects, and in most of them also the systemic arteriovenous oxygen difference, the total oxygen uptake and the pulmonary arterial and wedge pressures. 3. The infusion of indomethacin was followed by a decreased cardiac output (from 7.3 +/- 0.3 to 6.3 +/- 0.3 litres/min) and an increased mean systemic blood pressure (from 92 +/- 1 to 102 +/- 1 mmHg), indicating an elevation of the total systemic vascular resistance (from 98 +/- 4 to 124 +/- 5 kPa 1(-1) s) by indomethacin. The ventilation and the pulmonary vascular resistance did not change after the infusion of indomethacin. 4. The results suggest that products formed by the cyclo-oxygenase system at rest exert a relaxing effect in certain parts of the systemic vascular bed, thereby lowering the systemic vascular resistance.

Adult↗
PubMed1978

Effects of nicotine on cardiac prostaglandin and platelet thromboxane synthesis.

1 Rabbit hearts were perfused with a solution containing [14C]-arachidonic acid (AA) and various concentrations of nicotine (3 x 10(-8) to 3 x 10(-5) M). The venous effluent was collected and extracted for lipid acid material, which was subsequently subjected to thin layer radiochromatography. 2 Human platelets were incubated with nicotine (10(-8) to 10(-4) M), in the absence or presence of unlabelled AA. The amount of smooth muscle stimulating activity resulting from 30s of incubation was tested on a rabbit aortic strip. 3 In hearts perfused with [14C]-AA; nicotine induced a dose-related depression of the release of [14C]-6-keto-prostaglandin F1alpha, and a parallel increase of [14C]-prostaglandin E2. 4 Nicotine neither induced synthesis of thromboxane in human platelets, nor affected the platelet synthesis of thromboxane induced by AA. 5 It is suggested that nicotine affects the metabolism of prostaglandin endoperoxides in the heart by inhibiting their conversion to prostacyclin and facilitating, directly or indirectly, the formation of prostaglandin E2.

Animals↗
PubMed1978

Prostaglandin-mediated inhibition of noradrenaline release: II. Dual mechanism behind its frequency-dependence.

Sympathetically innervated, isolated rabbit hearts were perfusated according to Langendorff and the nerves were stimulated at 2, 5 or 10 Hz by equally long trains of pulses. The outflows of prostaglandin-like substances (PLS) and of noradrenaline (NA), induced by the nerve stimulations, were followed. The sensitivity of the process of NA release to exogenous PGE1 (2--6 X 10--8 M) at 2, 5 and 10 Hz was assayed. The outflow of PLS was found to be frequency-dependent, being greater at 2 Hz than at higher discharge rates, while the outflow of NA was similar at the different frequencies. The inhibitory action of PGE1 on the NA release process was more pronounced at 2 than at 10 Hz. It is concluded that the frequency-dependence of the endogenous PGE-mediated inhibition of the release of NA from discharging sympathetic nerves is based on 2 independent, frequency-related mechanisms: a) a higher synthesis rate of PLS/impulse, and b) a more pronounced sensitivity of the process of NA release, at low compared to higher impulse frequences.

Animals↗
PubMed1978

Influence of indomethacin and of prostaglandin E1 on total and regional blood flow in man.

The central and regional circulatory effects in man of the prostaglandin synthetase inhibitor indomethacin and of prostaglandin E1 (PGE1) were studied. Systemic blood pressure, cardiac output, and renal and splanchnic blood flow were measured at rest, following infusion of indomethacin (50 mg i.v.), and during infusion of PGE1 (4--8 mg x min-1 i.v.) after the administration of indomethacin. An increase in the total systemic resistance (+ 20%), as well as in the renal (+ 30%) and splanchnic (+ 16%) vascular resistances developed rapidly following the administration of indomethacin. Infusion of PGE1 completely restored the resistance in the renal and splanchnic regions, and in addition markedly increased the blood flow in non-visceral tissues. We suggest that the circulatory effects by indomethacin are elicited via the drug's inhibitory effect on prostaglandin synthetase in the vessel walls, and that vasodilating products of PG synthetase affect the regional blood flow distribution in man.

Adult↗