Markers of microbial translocation predict hypertension in HIV-infected individuals.

OBJECTIVES: The aim of the study was to test the hypothesis that microbial translocation, quantified by levels of lipopolysaccharide (LPS) and subsequent monocyte activation [soluble (sCD14)], is associated with hypertension in HIV-infected individuals. METHODS: In this exploratory substudy, 42 patients were recruited from a larger, longitudinal HIV-infected cohort study on blood pressure. LPS and sCD14 levels were measured retrospectively at the time of nadir CD4 cell count, selecting untreated HIV-infected patients with both advanced immunodeficiency and preserved immunocompetence at the time of nadir. Patients with later sustained hypertension (n = 16) or normotension (n = 26) throughout the study were identified. LPS was analysed using the Limulus Amebocyte Lysate colorimetric assay (Lonza, Walkersville, MD) and sCD14 using an enzyme-linked immunosorbent assay (ELISA). Nonparametric statistical tests were applied. RESULTS: In the HIV-infected patients [median (interquartile range) age 42 (32-46) years; 79% male and 81% Caucasian], LPS and sCD14 levels were both negatively correlated with nadir CD4 cell count. Plasma levels of LPS (P < 0.001) and sCD14 (P = 0.024) were elevated in patients with later hypertension compared with patients with normotension. There was a stepwise increase in the number of patients with hypertension across tertiles of LPS (P = 0.001) and sCD14 (P = 0.007). Both LPS and sCD14 were independent predictors of elevated blood pressure after adjustment for age and gender. For each 10-unit increase in LPS (range 66-272 pg/ml), the increment in mean blood pressure in the first period of blood pressure recording was 0.86 (95% confidence interval 0.31-1.41) mmHg (P = 0.003). CONCLUSIONS: As LPS and sCD14 were both independently associated with elevated blood pressure, microbial translocation may be linked to the development of hypertension.

Association between HIV infection and attenuated diurnal blood pressure rhythm in untreated hypertensive individuals.

OBJECTIVE: Hypertensive cardiovascular complications are more closely associated with ambulatory blood pressure (ABP), particularly the attenuated diurnal blood pressure (BP) rhythm (i.e. a fall in systolic blood pressure <10% during the night compared with the day), than with casual BP. The aim of the study was to assess the ABP pattern in an HIV-infected cohort in which hypertension was newly diagnosed. METHODS: ABP over 24 h was compared between 77 newly diagnosed, untreated hypertensive HIV-positive individuals and 76 HIV-uninfected untreated hypertensive controls. RESULTS: More HIV-infected subjects had an attenuated ABP rhythm with a reduced nocturnal fall than HIV-negative hypertensive control subjects (60 vs. 33%, respectively; P=0.001). The dipping pattern was observed despite newly diagnosed hypertension, a low prevalence of microalbuminuria, and the absence of signs of overt kidney disease. Furthermore, the prevalence of nondipping in the HIV-infected subjects was independent of combination antiretroviral treatment. Multiple logistic regression analysis with dipping pattern as the dependent variable showed that HIV status was an independent predictor of nondipping BP [P=0.002; odds ratio (OR) 0.33; 95% confidence interval (CI) 0.17-0.66]; casual SBP (P=0.37; OR 1.001; 95% CI 0.99-1.04) and microalbuminuria (P=0.39; OR 1.56; 95% CI 0.57-4.28) were not associated with dipping pattern. CONCLUSIONS: The prevalence of a nondipping BP pattern in HIV-infected subjects with newly diagnosed hypertension who had not received antihypertensive treatment was high and significantly greater than in hypertensive control subjects.

Basal hyperchlorhydria and its relation to the plasma concentrations of secretin, vasoactive intestinal polypeptide (VIP) and gastrin during prolonged strain.

Twenty young men divided into two groups participated in a five day training course with prolonged and heavy physical exercise, calorie supply deficiency and severe sleep deprivation. Basal acid output (BAO) was measured immediately after the course in seven of ten subjects who were given placebo tablets (placebo group) and in four of ten subjects who had a daily intake of 1 g cimetidine (cimetidine-group) during the course. Median BAO increased 3-fold in the placebo subjects (from 2.7 mmol/h to 8.2 mmol/h) but showed no increase in the cimetidine treated subjects. The median fasting plasma concentrations of secretin increased 2-8-fold during the course. Gastric suction for 1 h or ingestion of cimetidine reduced the plasma concentration of secretin by approx. 50%. Vasoactive intestinal polypeptide (VIP) increased 2-fold and was not influenced by reduction of gastric acid. The placebo group showed a small increase (P less than 0.05) in plasma concentration of gastrin on day two during the course. The study shows a marked hyperchlorhydria which partly explains the fasting hypersecretinemia found during prolonged strain. This strain-induced hyperchlorhydria could be abolished by treatment with the selective H2-receptor antagonist cimetidine.

Increased plasma response of gastric inhibitory polypeptide to oral glucose and a liquid meal after prolonged starvation in healthy man.

24 young, military subjects participated in a ranger training course of 5 days' duration with prolonged, heavy physical exercise and sleep deprivation. The subjects were divided into two groups showing either large calorie deficiency or nearly isocaloric status. An oral glucose tolerance test was performed on the subjects on day 5 on the course and in a control experiment 8 weeks after the course. During the course the subjects with negative calorie balance showed augmented integrated glucose-induced gastric inhibitory polypeptide (GIP) response (p less than 0.05) and the plasma concentration of GIP after glucose stimulation was higher at 90 and 120 min during the course than in the control experiment. On the other hand, the plasma GIP levels of the subjects on isocaloric diet changed similarly during the experimental period and the control period. In another experiment 11 healthy subjects were given a meal after an overnight fast and after 5 days of absolute fasting. The 5-day fast provoked higher postprandial plasma concentration of GIP between 60 and 150 min after meal stimulation, and the integrated meal-stimulated GIP response increased (p less than 0.01) after the prolonged fasting. The subjects in both experiments showed glucose intolerance. The insulinogenic index decreased during the training course, but increased during the prolonged, absolute fasting. The study shows that there is a dietary modulation of the GIP response to nutrient stimulation in healthy man and that the augmented GIP release is not attributable to insulin release.

Secretin--a new stress hormone?

The plasma concentration of secretin was measured during a 5-day military training course comprising prolonged physical exercise (35% of max O2 uptake), severe caloric deficiency (approx. 35700 kJ/24 h) and sleep deprivation (only 2 h of sleep as a total during 5 days). 24 subjects were divided into 3 groups, one group was compensated for the caloric deficiency and another group was partly compensated for the sleep deprivation. The results showed that the fasting plasma secretin increased 3-6-fold (from 1.8-3.7 to 13.3-19.1 pmol/l) during the course with small differences in increase between the groups. Ingestion of a mixed meal reduced the fasting plasma secretin by about 40% during the course, while oral glucose reduced the plasma secretin to the concentrations found in the control experiment. The study shows that plasma secretin is increased when man is exposed to prolonged multifactorial stress. Additional food or sleep appears to have small influence on the fasting plasma secretin, but after giving a meal or oral glucose solution the plasma secretin decreases rapidly.

hPP and gastrin response to a liquid meal and oral glucose during prolonged severe exercise, caloric deficit, and sleep deprivation.

Sixteen young healthy military cadets were subjected to prolonged severe exercise, caloric supply deficiency, and sleep deprivation during a 5-day ranger training course. Several cadets complained of gastric discomfort. The fasting and postprandial human pancreatic polypeptide (hPP) and gastrin levels induced by a liquid meal (no. = 9) and peroral glucose load (no. = 7) were measured during normal school activities (control) and on the third day during the course. The results showed that the fasting level of hhPP was significantly increased during the course. Both during meal and glucose stimulation the hPP level during the course was significantly higher at most registrations than during control conditions. The fasting level of gastrin was not changed. The maximal level of gastrin during meal stimulation was higher during the course than during the control period. Glucose loading, on the other hand, did not change the gastrin response. The integrated response of hPP and gastrin were not changed during the course either for the liquid meal or for the peroral glucose load.