Key pointsr Weightlessness in space induces initially an increase in stroke volume and cardiac output, accompanied by unchanged or slightly reduced blood pressure.r It is unclear whether these changes persist throughout months of flight. r Here, we show that cardiac output and stroke volume increase by 35-41% between 3 and 6 months on the International Space Station, which is more than during shorter flights.r Twenty-four hour ambulatory brachial blood pressure is reduced by 8-10 mmHg by a decrease in systemic vascular resistance of 39%, which is not a result of the suppression of sympathetic nervous activity, and the nightly dip is maintained in space.r It remains a challenge to explore what causes the systemic vasodilatation leading to a reduction in blood pressure in space, and whether the unexpectedly high stroke volume and cardiac output can explain some vision acuity problems encountered by astronauts on the International Space Station.Abstract Acute weightlessness in space induces a fluid shift leading to central volume expansion. Simultaneously, blood pressure is either unchanged or decreased slightly. Whether these effects persist for months in space is unclear. Twenty-four hour ambulatory brachial arterial pressures were automatically recorded at 1-2 h intervals with portable equipment in eight male astronauts: once before launch, once between 85 and 192 days in space on the International Space Station and, finally, once at least 2 months after flight. During the same 24 h, cardiac output (rebreathing method) was measured two to five times (on the ground seated), and venous blood was sampled once (also seated on the ground) for determination of plasma catecholamine concentrations. The 24 h average systolic, diastolic and mean arterial pressures (mean ± SE) in space were reduced by 8 ± 2 mmHg (P = 0.01; ANOVA), 9 ± 2 mmHg (P < 0.001) and 10 ± 3 mmHg (P = 0.006), respectively. The nightly blood pressure dip of 8 ± 3 mmHg (P = 0.015) was maintained. Cardiac stroke volume and output increased by 35 ± 10% and 41 ± 9% (P < 0.001); heart rate and catecholamine concentrations were unchanged; and systemic vascular resistance was reduced by 39 ± 4% (P < 0.001). The increase in cardiac stroke volume and output is more than previously observed during short duration flights and might be a precipitator for some of the vision problems encountered by the astronauts. The spaceflight vasodilatation mechanism needs to be explored further.

-The present experiments were performed to elucidate the acute effects of intravenous infusion of glucagon-like peptide (GLP)-1 on central and renal hemodynamics in healthy men. Seven healthy middle-aged men were examined on two different occasions in random order. During a 3-h infusion of either GLP-1 (1.5 pmol·kg Ϫ1 ·min Ϫ1 ) or saline, cardiac output was estimated noninvasively, and intraarterial blood pressure and heart rate were measured continuously. Renal plasma flow, glomerular filtration rate, and uptake/release of hormones and ions were measured by Fick's Principle after catheterization of a renal vein. Subjects remained supine during the experiments. During GLP-1 infusion, both systolic blood pressure and arterial pulse pressure increased by 5 Ϯ 1 mmHg (P ϭ 0.015 and P ϭ 0.002, respectively). Heart rate increased by 5 Ϯ 1 beats/min (P ϭ 0.005), and cardiac output increased by 18% (P ϭ 0.016). Renal plasma flow and glomerular filtration rate as well as the clearance of Na ϩ and Li ϩ were not affected by GLP-1. However, plasma renin activity decreased (P ϭ 0.037), whereas plasma levels of atrial natriuretic peptide were unaffected. Renal extraction of intact GLP-1 was 43% (P Ͻ 0.001), whereas 60% of the primary metabolite GLP-1 9-36amide was extracted (P ϭ 0.017). In humans, an acute intravenous administration of GLP-1 leads to increased cardiac output due to a simultaneous increase in stroke volume and heart rate, whereas no effect on renal hemodynamics could be demonstrated despite significant extraction of both the intact hormone and its primary metabolite.glucagon-like peptide-1; blood pressure; heart rate; cardiac output; renal plasma flow GLUCAGON-LIKE PEPTIDE (GLP)-1 is a 30-amino acid peptide hormone primarily synthesized by enteroendocrine L cells distributed in the small and large intestines and secreted in a nutrient-dependent manner. GLP-1 stimulates insulin secretion and inhibits glucagon secretion and gastric emptying, resulting in reduced postprandial glycemia (14). The GLP-1 receptor is a G protein-coupled receptor and a member of the glucagon receptor family (18). The GLP-1 receptor was originally identified in islet ␤-cells in the pancreas, but it is also widely expressed in extrapancreatic tissues in humans (17,25,33).GLP-1 receptor agonists have been approved for the treatment of hyperglycemia in subjects with diabetes, and, in addition, they may have significant cardiovascular effects (6, 28). However, results regarding the effects on arterial blood pressure are conflicting (2, 9, 11, 20 -22, 29, 31). The reasons for the apparent discrepancies are not clear, although differences between species, doses applied, and durations of treatment may contribute.Human studies have reported a natriuretic effect of native GLP-1, possibly due to reduced Na ϩ reabsorption in the proximal tubule (12,29). However, in a recent study (25) validating a new, monoclonal GLP-1 receptor antibody, GLP-1 receptors could not be identified in the proximal tubule, whereas they were expressed in renin-secreting ...

A truncated form of human glucose-dependent insulinotropic polypeptide (GIP), GIP(3-30)NH, was recently identified as an antagonist of the human GIP receptor. This study examined the ability of GIP(3-30)NH to antagonize the physiological actions of GIP in glucose metabolism, subcutaneous abdominal adipose tissue blood flow (ATBF), and lipid metabolism in humans. Eight lean subjects were studied by measuring arteriovenous concentrations of metabolites and ATBF on three different occasions during hyperglycemic-hyperinsulinemic clamps with concomitant infusions of GIP, GIP(3-30)NH, or both GIP and GIP(3-30)NH During infusion of GIP(3-30)NH alone and in combination with GIP, insulin levels and the total glucose amount infused to maintain the clamp were lower than during GIP alone. In addition, ATBF remained constant during the antagonist and increased only slightly in combination with GIP, whereas it increased fivefold during GIP alone. Adipose tissue triacylglyceride (TAG) and glucose uptake decreased, and the free fatty acid/glycerol ratio increased during the antagonist alone and in combination with GIP. The changes in glucose infusion rates and plasma insulin levels demonstrate an inhibitory effect of the antagonist on the incretin effect of GIP. In addition, the antagonist inhibited GIP-induced increase in ATBF and decreased the adipose tissue TAG uptake, indicating that GIP also plays a crucial role in lipid metabolism.

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