cyclic-gmp and Hypotension--Orthostatic

This investigation was conducted to test the following hypotheses: 1) If simulated orthostasis (LBNP) reduces plasma cGMP; 2) if simulated microgravity alters any such LBNP-induced effect; and 3) if simulated microgravity reduces resting plasma cGMP levels. In addition, we studied the time-course of thoracic impedance during, LBNP and asked if there is heart rate/blood pressure reduction after LBNP. During real and simulated spaceflight, blood is re-distributed throughout the vasculature along the body axis, vascular mechanoreceptor loads are altered, "excess" fluid is lost from the organism, and reflexly connected endocrine systems adapt with accompanying changes of hormone output. Altered steady-state plasma concentrations of volume sensitive hormones have been observed inflight as well as postflight. Hormones play a salient role in volume regulation but have barely been studied during microgravitational conditions in conjunction with lower body suction (LBNP). We used LBNP as an analogue to orthostatic stress since this model is useful to investigate, on quantitative grounds, hormone concentration changes as a function of cardiovascular stress in simulated weightless conditions. Earlier we reported consistently reduced plasma ANP and cGMP levels in a case study (14 mo spaceflight); transient hormonal changes after LBNP (as % of pre-LBNP values) were not different (p>0.05) from ground-control findings, and other hormone levels did not consistently deviate from ground control values. This is important since transmural central venous pressure which influences ANP output from the heart, and is elevated despite decreased CVP in parabolic flight, might be downregulated on a long-term basis. TCVP has not yet been measured inflight.

Topics: Bed Rest; Blood Pressure; Cardiography, Impedance; Cyclic GMP; Head-Down Tilt; Heart Rate; Humans; Hypotension, Orthostatic; Lower Body Negative Pressure; Male; Weightlessness Simulation

Plasma atrial natriuretic factor (ANF) concentrations are increased in subjects with insulin-dependent diabetes mellitus (IDDM). A potential contribution of ANF to the maintenance of abnormalities in renal hemodynamic function has been considered but not proven in human diabetic subjects. The aim of these experiments was to determine the response of renal blood flow (RBF), glomerular filtration rate (GFR), filtration fraction (FF), and urinary sodium excretion (UNaV) to a reduction of plasma ANF concentrations induced by application of nonhypotensive lower body negative pressure (LBNP) in a group of subjects with early, uncomplicated, well-controlled IDDM compared with control subjects. Baseline supine measurements before LBNP revealed the diabetic subjects to have a significantly higher plasma ANF (31 +/- 2 vs. 24 +/- 2 pg/ml, P = 0.05). GFR tended to be higher (118 +/- 11 vs. 104 +/- 9 ml/min) and UNaV tended to be depressed (188 +/- 25 vs. 240 +/- 25 mumol/min) despite equal sodium intake, but not significantly so. In addition IDDM subjects exhibited significantly lower baseline plasma norepinephrine (PNE) concentrations (0.91 +/- 0.20 vs. 1.60 +/- 0.2 nmol/l, P = 0.03). Forearm vascular resistance (FVR) was not significantly different between the two groups (29 +/- 5 vs. 33 +/- 5 units). LBNP induced comparable decreases in ANF and central venous pressure (CVP) in both groups. The anticipated renal response to ANF reduction (declines in GFR, FF, and UNaV) occurred only in the normal control group. The percent decline in GFR (11% vs. 34.5%, P = 0.01) was markedly attenuated in IDDM subjects. The expected reflexive increase in PNE and FVR also did not occur in IDDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Blood Pressure; Cyclic GMP; Diabetes Mellitus, Type 1; Diastole; Forearm; Glomerular Filtration Rate; Heart Rate; Humans; Hypotension, Orthostatic; Male; Muscles; Norepinephrine; Reference Values; Renal Circulation; Renin; Sodium; Supine Position; Systole; Time Factors; Vascular Resistance