Allelic variation for alpha-Glucan Water Dikinase is associated with starch phosphate content in tetraploid potato.

KEY MESSAGE: Association analysis resulted in the identification of specific StGWD alleles causing either an increase or decrease in starch phosphate content which was verified in diploid and tetraploid potato mapping populations. Potatoes are grown for various purposes like French fries, table potatoes, crisps and for their starch. One of the most important aspects of potato starch is that it contains a high amount of phosphate ester groups which are considered to be important for providing improved functionalization after derivatization processes. Little is known about the variation in phosphate content as such in different potato varieties and thus we studied the genetic diversity for this trait. From other studies it was clear that the phosphate content is controlled by a quantitative trait locus (QTL) underlying the candidate gene α-Glucan Water Dikinase (StGWD) on chromosome 5. We performed direct amplicon sequencing of this gene by Sanger sequencing. Sequences of two StGWD amplicons from a global collection of 398 commercial cultivars and progenitor lines were used to identify 16 different haplotypes. By assigning tag SNPs to these haplotypes, each of the four alleles present in a cultivar could be deduced and linked to a phosphate content. A high value for intra-individual heterozygosity was observed (Ho = 0.765). The average number of different haplotypes per individual (Ai) was 3.1. Pedigree analysis confirmed that the haplotypes are identical-by-descent (IBD) and offered insight in the breeding history of elite potato germplasm. Haplotypes originating from introgression of wild potato accessions carrying resistance genes could be traced. Furthermore, association analysis resulted in the identification of specific StGWD alleles causing either an increase or decrease in starch phosphate content varying from 12 nmol PO4/mg starch to 38 nmol PO4/mg starch. These allele effects were verified in diploid and tetraploid mapping populations and offer possibilities to breed and select for this trait.

QTL mapping in diploid potato by using selfed progenies of the cross S. tuberosum × S. chacoense.

Usually, mapping studies in potato are performed with segregating populations from crosses between highly heterozygous diploid or tetraploid parents. These studies are hampered by a high level of genetic background noise due to the numerous segregating alleles, with a maximum of eight per locus. In the present study, we aimed to increase the mapping efficiency by using progenies from diploid inbred populations in which at most two alleles segregate. Selfed progenies were generated from a cross between S. tuberosum (D2; a highly heterozygous diploid) and S. chacoense (DS; a homozygous diploid clone) containing the self-incompatibility overcoming S locus inhibitor (Sli-gene). The Sli-gene enables self-pollination and the generation of selfed progenies. One F2 population was used to map several quality traits, such as tuber shape, flesh and skin color. Quantitative trait loci were identified for almost all traits under investigation. The identified loci partially coincided with known mapped loci and partially identified new loci. Nine F3 populations were used to validate the QTLs and monitor the overall increase in the homozygosity level.

Advanced Thomson scattering system for high-flux linear plasma generator.

An advanced Thomson scattering system has been built for a linear plasma generator for plasma surface interaction studies. The Thomson scattering system is based on a Nd:YAG laser operating at the second harmonic and a detection branch featuring a high etendue (f/3) transmission grating spectrometer equipped with an intensified charged coupled device camera. The system is able to measure electron density (n(e)) and temperature (T(e)) profiles close to the output of the plasma source and, at a distance of 1.25 m, just in front of a target. The detection system enables to measure 50 spatial channels of about 2 mm each, along a laser chord of 95 mm. By summing a total of 30 laser pulses (0.6 J, 10 Hz), an observational error of 3% in n(e) and 6% in T(e) (at n(e) = 9.4 × 10(18) m(-3)) can be obtained. Single pulse Thomson scattering measurements can be performed with the same accuracy for n(e) > 2.8 × 10(20) m(-3). The minimum measurable density and temperature are n(e) < 1 × 10(17) m(-3) and T(e) < 0.07 eV, respectively. In addition, using the Rayleigh peak, superimposed on the Thomson scattered spectrum, the neutral density (n(0)) of the plasma can be measured with an accuracy of 25% (at n(0) = 1 × 10(20) m(-3)). In this report, the performance of the Thomson scattering system will be shown along with unprecedented accurate Thomson-Rayleigh scattering measurements on a low-temperature argon plasma expansion into a low-pressure background.

Evaluation of biomarkers for cardiotoxicity of anthracyclin-based chemotherapy.

INTRODUCTION: The clinical assessment of the myocardial damage caused by anthracyclin (ANT)-therapy is difficult. Therefore a study was performed to evaluate non-invasive markers of anthracyclin-induced cardiac effects, with emphasis on course-to-course variation. METHODS: Eligible for study participation were patients, without known cardiologic abnormalities who did not use cardiotoxic medication (except for ANT-therapy), who had previously completed at least three cycles of anthracyclin-containing chemotherapy (n = 14) and patients who were ANT-naïve and who were scheduled to receive doxorubicin-containing chemotherapy (n = 12). Seven patients in this last group also completed at least three cycles and were available for follow-up assessments; thus a total population of 21 patients (12F/9M) completed at least three courses ANT-chemotherapy. In these patients blood samples and ECG-recordings were taken within 6 months after completion of ANT-therapy. In 12 patients (10F/2M) assessments were also done before, immediately afterwards and at 24 h after each course of ANT. RESULTS AND CONCLUSIONS: In the patients who completed chemotherapy, NT-proBNP was 277% (n = 21; 95% CI: 86-661%, P < 0.001) higher compared to healthy volunteers. During the first course NT-proBNP rose 269% (n = 12; 167-409%, P < 0.0001) at 24 h post-administration. The linear corrected QT (QTcL) directly after the first administration of ANT increased by 9.56 ms (n = 12; 3.85-15.27, P < 0.001) and this prolongation was still present at 24 h, 11.48 ms (n = 12; 5.61-17.34, P < 0.0001). Both NT-proBNP and QTcL returned to baseline before the start of the next course and a similar pattern was observed during each course. NT-proBNP and QTcL may be useful markers for course-to-course evaluation of anthracyclin-induced cardiotoxicity.

Construction of a potato transcriptome map based on the cDNA-AFLP technique.

The cDNA-AFLP technique can be used to monitor differential gene expression, but also for linkage mapping. Extending previous works, we have now constructed an integrated linkage map of the potato transcriptome based on the said technique that has a length of around 800 cM and contains nearly 700 transcriptome derived fragments (TDFs). At the same time, most of these markers are anchored to the bins of a highly saturated reference map in potato, combining in this way the information provided by different marker types. Moreover, we detected and confirmed an elevated degree of allelic fragments with this marker type, which was present in nearly half of all primer combinations and involved around 20% of all fragments. These properties were particularly useful to establish anchor points for integrating the individual parental linkage maps. Comparative expression profiling in different plant materials revealed that only a few additional TDFs were obtained which were specific for mature leaves or tubers compared to the TDFs present in whole in vitro plants. Since TDF markers are derived from coding regions, they generally also represent sequences with a biological function. In four case studies, co-migrating TDFs in different Solanum wild species always represented potential alleles based on elevated homologies among them. Two resistance gene homologs were identified by analysing TDFs, which were co-located with known QTLs.

Characterization and high-resolution mapping of a late blight resistance locus similar to R2 in potato.

Identification of resistance (R) genes to Phytophthora infestans is an essential step in molecular breeding of potato. We identified three specific R genes segregating in a diploid mapping population. One of the R genes is located on chromosome 4 and proved phenotypically indistinguishable from the Solanum demissum-derived R2, although S. demissum is not directly involved in the pedigree of the population. By bulked segregant analysis combined with a resistance assay, a genetic linkage map of the R2-like locus was constructed with 30 coupling and 23 repulsion phase AFLP markers. Two markers flanking the R2-like locus were applied to screen an extended population of 1,586 offspring. About 103 recombinants were selected, and an accurate high-resolution map was constructed. The R2-like resistance was localized in a 0.4 cM interval and was found co-segregating with four AFLP markers, which can be used to isolate the R2-like gene by map-based gene cloning. By analyzing race-specificity and R gene-specific molecular markers, we also found that an R1-like gene and an additional unknown R gene are segregating in the population.

Genetic diversity of taro, Colocasia esculenta (L.) Schott, in Southeast Asia and the Pacific.

The genetic diversity of 255 taro (Colocasia esculenta) accessions from Vietnam, Thailand, Malaysia,Indonesia, the Philippines, Papua New Guinea and Vanuatu was studied using AFLPs. Three AFLP primer combinations generated a total of 465 scorable amplification products. The 255 accessions were grouped according to their country of origin, to their ploidy level (diploid or triploid) and to their habitat--cultivated or wild. Gene diversity within these groups and the genetic distance between these groups were computed. Dendrograms were constructed using UPGMA cluster analysis. In each country, the gene diversity within the groups of wild genotypes was the highest compared to the diploid and triploid cultivars groups. The highest gene diversity was observed for the wild group from Thailand (0.19), the lowest for the diploid cultivars group from Thailand(0.007). In Malaysia there was hardly any difference between the gene diversity of the cultivars and wild groups, 0.07 and 0.08, respectively. The genetic distances between the diploid cultivars groups ranges from 0.02 to 0.10, with the distance between the diploid accessions from Thailand and Malaysia being the highest. The genetic distances between the wild groups range from 0.05 to 0.07. First, a dendrogram was constructed with only the diploids cultivars from all countries. The accessions formed clusters largely according to the country from which they originated. Two major groups of clusters were revealed, one group assembling accessions from Asian countries and the other assembling accessions from the Pacific. Surprisingly, the group of diploid cultivars from Thailand clustered among the Pacific countries. Secondly,a dendrogram was constructed with diploid cultivated,triploid cultivated and wild accessions. Again the division of the accessions into an Asian and a Pacific gene pool is obvious. The presence of two gene pools for cultivated diploid taro has major implications for the breeding and conservation of germplasm.

Can the QTL for late blight resistance on potato chromosome 5 be attributed to foliage maturity type?

We investigated the association between late blight resistance and foliage maturity type in potato by means of molecular markers. Two QTLs were detected for foliage resistance against Phytophthora infestans (on chromosomes 3 and 5) and one for foliage maturity type (on chromosome 5). The QTL for resistance to late blight and the QTL for foliage maturity type on chromosome 5 appeared to be mapped on indistinguishable positions. We were interested whether this genetic linkage was due to closely linked but different genes, or due to one (or more) gene(s) with pleiotropic effects. We therefore developed an approach to detect QTLs, in which resistance to late blight was adjusted for foliage maturity type. This analysis revealed the same two QTLs for resistance against P. infestans, but the effect of the locus on chromosome 5 was reduced to only half the original effect. This is a strong indication that the two indistinguishable QTLs for foliage maturity type and for late blight resistance on chromosome 5 may actually be one gene with a pleiotropic effect on both traits. However, there was still a significant effect on resistance against P. infestans on the locus on chromosome 5 after adjusting for foliage maturity type. Therefore we cannot rule out the presence of two closely linked QTLs on chromosome 5: one with a pleiotropic effect on both late blight resistance and foliage maturity type, and another with merely an effect on resistance. In addition, the two QTLs for resistance to late blight showed an important epistatic interaction, suggesting that QTLs for resistance affect each other's expression.

Fiducial segment averaging to improve cardiac time interval estimates.

To improve the accuracy of fiducial point estimates, a technique was developed and tested that uses the coherence of relatively small segments within the P-QRS-T complex from beat to beat. The methodology is applied to digitally stored electrocardiogram traces from various sources. It can be applied to single or multiple leads. First, the individual QRS complexes are identified with a matched filter technique. The trigger time points obtained are fine-adjusted by cross-correlating in turn each individual complex with the average of the remainder complexes and then shifting the complex till maximum correlation is achieved. The process is repeated till no improvement can be attained. Then the individual fiducial points are identified and a similar fine-adjustment is made to the individual points with a segment of approximately 60 ms around the fiducial point. This process is performed in turn for P-onset, QRS-onset and offset, peak of T wave and end of T wave. The values of PR-interval, QRS-duration and QT follow from these measurements. The validity of the result can be assessed by visual inspection and by examining the standard deviation of the measurements obtained. From the above intervals, it is generally accepted that QRS-duration is fairly constant over a short recording duration, whereas PR and QT are inherently heart-rate dependent. Often a linear regression of QT onto RR can be calculated with a significant correlation coefficient, indicating a physiological QT/RR relationship in these recordings of relative short duration. It would be impossible to show this last relationship if the individual QT changes had not been preserved by the technique described.

Linkage analysis by genotyping of sibling populations: a genetic map for the potato cyst nematode constructed using a "pseudo-F2" mapping strategy.

A mapping strategy is described for the construction of a linkage map of a non-inbred species in which individual offspring genotypes are not amenable to marker analysis. After one extra generation of random mating, the segregating progeny was propagated, and bulked populations of offspring were analyzed. Although the resulting population structure is different from that of commonly used mapping populations, we show that the maximum likelihood formula for a normal F2 is applicable for the estimation of recombination. This "pseudo-F2" mapping strategy, in combination with the development of an AFLP assay for single cysts, facilitated the construction of a linkage map for the potato cyst nematode Globodera rostochiensis. Using 12 pre-selected AFLP primer combinations, a total of 66 segregating markers were identified, 62 of which were mapped to nine linkage groups. These 62 AFLP markers are randomly distributed and cover about 65% of the genome. An estimate of the physical size of the Globodera genome was obtained from comparisons of the number of AFLP fragments obtained with the values for Caenorhabditis elegans. The methodology presented here resulted in the first genomic map for a cyst nematode. The low value of the kilobase/centimorgan (kb/cM) ratio for the Globodera genome will facilitate map-based cloning of genes that mediate the interaction between the nematode and its host plant.

Use of allele specificity of comigrating AFLP markers to align genetic maps from different potato genotypes.

The allele specificity of AFLP markers was assessed in five relatively unrelated potato genotypes. To this end, two diploid mapping populations of potato, F1SH x RH and F1AM x RH, were analysed using four and six AFLP primer combinations, respectively, recently applied to the analysis of the genetically well characterized backcross population BC_C x E. The AFLP profiles of the five parents revealed 733 AFLP markers and, when identical primer combinations were used, 131 comigrating AFLP markers were identified. After construction of five parental maps, the genomic positions of these comigrating AFLP markers were compared and 117 markers (89%) which targeted the same genomic region were assumed to be homologous. Of these putative homologues, 20 markers, each cloned from at least two genotypes, were sequenced and 19 sets of amplification products were shown to be nearly identical. The number of AFLP markers previously mapped in population BC_C x E ranged from three to eleven per chromosome, which allowed a reliable assessment of chromosome numbers from individual linkage groups obtained in populations F1SH x RH and F1AM x RH. The high incidence of corresponding AFLP alleles was confirmed by using an additional set of five primer combinations. The 733 AFLP markers localized provide a valuable reference collection for future mapping studies in potato. As a consequence AFLP analysis may replace more laborious locus-specific marker techniques.

A genetic map of potato (Solanum tuberosum) integrating molecular markers, including transposons, and classical markers.

A genetic map of potato (Solanum tuberosum L.) integrating molecular markers with morphological and isozyme markers was constructed using a backcross population of 67 diploid potato plants. A general method for map construction is described that differs from previous methods employed in potato and other outbreeding plants. First, separate maps for the female and male parents were constructed. The female map contained 132 markers, whereas the male map contained 138 markers. Second, on the basis of the markers in common the two integrated parental maps were combined into one with the computer programme JoinMap. This combined map consisted of 175 molecular markers, 10 morphological markers and 8 isozyme markers. Ninety-two of the molecular markers were derived from DNA sequences flanking either T-DNA inserts in potato or reintegrated maize transposable elements originating from these T-DNA constructs. Clusters of distorted segregation were found on chromosomes 1,2,8 and 11 for the male parent and chromosome 5 for both parents. The total length of the combined map is 1120 cM.

Multiple alleles for tuber shape in diploid potato detected by qualitative and quantitative genetic analysis using RFLPs.

Tuber shape in potato is commonly regarded as displaying continuous variation, yet at the diploid level phenotypes can be discerned visually, having round or long tubers. Inheritance of qualitative tuber shape can be explained by a single locus Ro, round being dominant to long. With restriction fragment length polymorphisms (RFLPs) the Ro locus was mapped on chromosome 10. Tuber shape was also studied as a quantitative trait, using the length/width ratio as trait value. The estimated broad sense heritability was h2 = 0.80. The morphologically mapped Ro locus explained 75% of the genetic variation, indicating the presence of a major quantitative trait locus (QTL) at the Ro locus and minor genetic factors. RFLP alleles linked with Ro alleles were used to divide the progeny into four genotypic classes: RofemaleRomale:Rofemalero:roRomale:roro = 1:1:1:1. The recessive ro allele is identical by descent in both parents. The significantly different effects (P = 0.0157) of the non-identical alleles Rofemale and Romale provided evidence for multiallelism at the Ro locus. Linkage mapping of the Ro locus was compared with QTL mapping. Only those markers which are polymorphic in both parents allow accurate QTL mapping when genetic factors segregate from both parents. This finding applies to QTL mapping in all outbreeders without homozygous inbred strains.

Identification and mapping of three flower colour loci of potato (S. tuberosum L.) by RFLP analysis.

The inheritance of flower colour in diploid potato (2 n = 2x = 24), was found to be controlled by three unlinked loci D, F and P. To determine the allelism with previously described loci and to dissect this oligogenic trait, a set of tester clones with well-defined genotypes was developed. By backcrossing the mapping population with these tester clones it was possible to obtain monogenic segregation ratios. These were required to detect linkage with RFLP loci and, despite distorted Mendelian ratios, the inheritance and mapping of the D, F and P loci could be unambiguously determined. Locus D, involved in the biosynthesis of red anthocyanins, was mapped on chromosome 2, while locus P, involved in the production of blue anthocyanins, was mapped on chromosome 11. Locus F, involved in the flower-specific expression of gene(s) accommodated by the D and P loci, was mapped on chromosome 10. The tester clones and the map position of the D, F and P loci may be of considerable value in simplifying the genetics of anthocyanin pigmentation.

Partial escape of angiotensin converting enzyme (ACE) inhibition during prolonged ACE inhibitor treatment: does it exist and does it affect the antihypertensive response?

OBJECTIVE: To investigate whether the compensatory rise in renin and plasma angiotensin I in response to repeated angiotensin converting enzyme (ACE) inhibitor treatment results in a partial escape of ACE inhibition over a 24-h dosing interval. DESIGN: A single-blind placebo-controlled study in two parallel groups of eight hypertensive subjects receiving a once-daily dose of the ACE inhibitor, spirapril, of either 12.5 or 25 mg. Detailed 24-h studies were performed at the end of 2 weeks of placebo, and after the first dose and 2 weeks administration of spirapril. METHODS: Twenty-four-hour ambulatory blood pressure was measured invasively. True' angiotensins I and II were measured by radioimmunoassay after high-performance liquid chromatography separation. RESULTS: Both for the lower and higher doses of spirapril, the time-course of changes of spiraprilat, the active metabolite of spirapril, and ACE activity was similar but the maximal rise in angiotensin I was twofold higher after 2 weeks administration than after the first dose. Angiotensin II after the first dose of spirapril fell rapidly, with lowest values 2 to 4 h after dosing. At the end of dosing interval angiotensin II had returned to values seen under placebo with the 12.5-mg dose, but at the end of the 24-h period it was still suppressed with the 25-mg dose. Compared with these first-dose responses the initial maximal degree of angiotensin II suppression after 2 weeks administration of either dose was similar, but during the subsequent hours the degree of angiotensin II suppression tended to be less with the lower and was significantly less with the higher dose of spirapril. With the lower dose of spirapril responses of 24-h ambulatory blood pressure to the first dose and to 2 weeks of administration were almost superimposable, although blood pressures in the second half of the dosing interval tended to be higher during chronic treatment. With the higher dose the response of nocturnal blood pressure after 2 weeks administration was diminished by 8.8 mmHg systolic and 6.8 mmHg diastolic. CONCLUSIONS: Repeated ACE inhibitor treatment with once-daily spirapril leads to a partial escape of ACE inhibition, as reflected by a shorter duration of angiotensin II suppression. This escape also affects the antihypertensive response in the second half of the dosing interval.

Prolonged blood pressure reduction by orally active renin inhibitor RO 42-5892 in essential hypertension.

OBJECTIVE: To investigate the effects of a novel specific renin inhibitor, RO 42-5892, with high affinity for human renin (Ki = 0.5 x 10(-9) mol/l), on plasma renin activity and angiotensin II concentration and on 24 hour ambulatory blood pressure in essential hypertension. DESIGN: Exploratory study in which active treatment was preceded by placebo. SETTING: Inpatient unit of teaching hospital. PATIENTS: Nine men with uncomplicated essential hypertension who had a normal sodium intake. INTERVENTIONS: Two single intravenous doses of RO 42-5892 (100 and 1,000 micrograms/kg in 10 minutes) given to six patients and one single oral dose (600 mg) given to the three others as well as to three of the patients who also received the two intravenous doses. RESULTS: With both intravenous and oral doses renin activity fell in 10 minutes to undetectably low values, while angiotensin II concentration fell overall by 80-90% with intravenous dosing and by 30-40% after the oral dose. Angiotensin II concentration was back to baseline four hours after the low and six hours after the high intravenous dose and remained low for at least eight hours after the oral dose. Blood pressure fell rapidly both after low and high intravenous doses and after the oral dose and remained low for hours. With the high intravenous dose the daytime (0900-2230), night time (2300-0600), and next morning (0630-0830) systolic blood pressures were significantly (p less than 0.05) lowered by 12.5 (95% confidence interval 5.6 to 19.7), 12.2 (5.4 to 19.3), and 10.7 (3.2 to 18.5) mm Hg respectively, and daytime diastolic pressure was lowered by 9.3 (2.2 to 16.8) mmHg. With the oral dose daytime, night time, and next morning systolic blood pressures were lowered by 10.3 (5.5 to 15.4), 10.5 (4.2 to 17.2), and 9.7 (4.0 to 15.6) mm Hg, and daytime and night time diastolic pressures were lowered by 5.8 (0.9 to 11.0) and 6.0 (0.3-12) mm Hg respectively. CONCLUSIONS: The effect of the inhibitor on blood pressure was maintained over a longer period than its effect on angiotensin II. RO 42-5892 is orally active and has a prolonged antihypertensive effect in patients who did not have sodium depletion. This prolonged effect seems to be independent, at least in part, of the suppression of circulating angiotensin II.

Comparison of the acute and chronic antihypertensive effect of two once-daily doses of spirapril by invasive twenty-four-hour ambulatory blood pressure monitoring.

Spirapril is a new non-sulphydryl angiotensin converting enzyme (ACE) inhibitor which is eliminated mainly through the liver. In a placebo-controlled study the acute and chronic (2 weeks) antihypertensive effects of two doses of spirapril (12.5 and 25 mg) were assessed by invasive 24-h ambulatory blood pressure monitoring in two groups of eight hypertensive subjects. After the first doses of 12.5 and 25 mg, blood pressure rapidly decreased, with a nadir after 4-6 h. At this time, mean arterial pressure was decreased by 24 +/- 2% with the 12.5 and 19 +/- 1% with the 25-mg dose. The antihypertensive response was sustained for almost the whole 24-h period with the 25-mg dose, but it was attenuated during the second half of the 24-h blood pressure monitoring with the 12.5-mg dose, leaving a residual antihypertensive effect of 6 +/- 2% 24 h after dosing. Compared with the response to the first dose, the antihypertensive response after 2 weeks of treatment was similar to that following the 12.5-mg dose, but with the 25-mg dose the response during the second half of the 24-h monitoring period, especially during the night, was attenuated. The reason for this attenuated antihypertensive response during prolonged ACE inhibition remains to be established.

Comparison of Finapres non-invasive beat-to-beat finger blood pressure with intrabrachial artery pressure during and after bicycle ergometry.

To evaluate the accuracy of continuous non-invasive blood pressure measurements in the finger during exercise, Finapres blood pressures of six normotensive healthy males were measured during increasing levels of bicycle exercise, using simultaneously registered ipsilateral intrabrachial artery pressures as a reference. At rest, finger systolic blood pressure was higher and finger diastolic and mean arterial pressures were lower than the corresponding intrabrachial pressures in five of the six subjects. During exercise, average finger diastolic and mean arterial pressures did not differ further from these intrabrachial pressures, but finger systolic pressure increased considerably more than the direct systolic pressure, exceeding it by 26 +/- 20 mmHg (mean +/- s.d.) at maximal exercise. This latter finding potentially limits the use of finger blood pressure measurements during exercise.

Twenty-four hour pressor effect of infused adrenaline in normotensive subjects: a randomized controlled double-blind cross-over study.

Stimulation of prejunctional beta 2-adrenoceptors on sympathetic nerve terminals increases vasoconstrictor nerve activity by facilitating release of noradrenaline. Therefore, man's endogenous beta 2-adrenoceptor agonist adrenaline has been implicated in the pathogenesis of hypertension. To test this hypothesis, adrenaline (15 mg/kg per min), noradrenaline (30 ng/kg per min) and saline (0.9% NaCl, 5.4 ml/h) were infused in 10 supine, resting healthy volunteers for 6 h (1000-1600 h) in random order 2 weeks apart in a double-blind crossover fashion. During infusion of noradrenaline and adrenaline, venous plasma concentrations rose to 705 +/- 58 (mean +/- s.e.m) and 230 +/- 28 pg/ml, respectively. Mean arterial pressure rose by 4% (P less than 0.001) during noradrenaline and fell by 5% (P less than 0.001) during the adrenaline infusion compared with the saline infusion. In the postinfusion period (1600-0900 h) mean arterial pressure was 7% higher (P less than 0.01) after adrenaline compared with the saline infusion, whereas after the noradrenaline infusion, values of mean arterial pressure were not different from those during the saline infusion. The pressor effect of adrenaline could not be explained by a central mechanism or by activation of the renin-angiotensin system. Thus, 'stress levels' of adrenaline mediate a delayed and protracted pressor effect. This is most likely due to stimulation of prejunctional beta 2-adrenoceptors, since 'stress levels' of noradrenaline are devoid of such activity. Our data support the 'adrenaline-hypertension' hypothesis in man.

Support for adrenaline-hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion.

In a double blind, crossover study 6 h infusions of adrenaline (15 ng/kg/min; 1 ng = 5.458 pmol), noradrenaline (30 ng/kg/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, "stress" levels of adrenaline (230 pg/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man.