WISE 2005: responses of women to sublingual nitroglycerin before and after 56 days of 6° head-down bed rest

Abstract

2012.-This study tested the hypothesis that cardiovascular effects of sublingual nitroglycerin (NG) would be exaggerated after 56 days of 6°head-down bed rest (HDBR) in women, and that an aerobic and resistive exercise countermeasure (EX, n ϭ 8) would reduce the effect compared with HDBR without exercise (CON, n ϭ 7). Middle cerebral artery maximal blood flow velocity (CBFV), cardiac stroke volume (SV), and superficial femoral artery blood flow (Doppler ultrasound) were recorded at baseline rest and for 5 min following 0.3 mg sublingual NG. Post-HDBR, NG caused greater increases in heart rate (HR) in CON compared with EX (ϩ24.9 Ϯ 7.7 and ϩ18.8 Ϯ 6.6 beats/min, respectively, P Ͻ 0.0001). The increase in HR combined with reductions in SV to maintain cardiac output. Systolic, mean, and pulse pressures were reduced 5-10 mmHg by NG, but total peripheral resistance was only slightly reduced at 3 min after NG. Reductions in CBFV of Ϫ12.5 Ϯ 3.8 cm/s were seen after NG, but a reduction in the Doppler resistance index suggested dilation of the middle cerebral artery with no differences after HDBR. The femoral artery dilated with NG and blood flow was reduced ϳ50% with the appearance of large negative waves suggesting a marked increase in downstream resistance, but there were no effects of HDBR. In general, responses of women to NG were not altered by HDBR; the greater increase in HR in CON but not EX was probably a consequence of cardiovascular deconditioning. These results contrast with the hypothesis and a previous investigation of men after HDBR by revealing no change in cardiovascular responses to exogenous nitric oxide. blood pressure; cerebral blood flow; Doppler ultrasound; nitroglycerin; hemodynamics; head-down bed rest; Women's International Simulation for Space Exploration-2005 Study THE VASODILATORY ACTIONS of nitric oxide (NO) work in conjunction with sympathetic vasoconstrictor activity and other vasoactive hormones in the regulation of blood pressure and blood flow (13,24). Acute alterations in NO effects on blood vessels have been noted under conditions that simulate spaceflight in animals (31, 36, 41, 44) and humans (5,7,30,34,35). These results suggest that alterations in hemodynamic responses with exposure to real or simulated microgravity may be due to changes in NO-mediated mechanisms.Animal models of simulated microgravity have shown elevated nitric oxide synthase (NOS) activity increasing NO production that could dilate peripheral vessels and reduce vascular responsiveness to norepinephrine (36,41). In contrast, cerebral arteries of hindlimb-suspended rats show reduced endothelial NOS (eNOS) protein (44) and reduced middle cerebral artery endothelium-dependent dilation (31). These results from animal studies point toward potential regional differences in hemodynamic responses to NO after simulated microgravity, a topic that has not been studied in humans.Focusing on isolated regions, studies involving humans suggest changes in the NO system after simulated microgravity. Expression of NOS isoforms in ...

Sodium nitroglycerin induces middle cerebral artery vasodilatation in young, healthy adults

“…Thus, a second major outcome of this study was the observation that, despite the increase in CSA after NTG and stable MAP, blood velocity decreased in the MCA such that overall CBF remained unchanged. This observation supports previous findings of reductions in MCA blood velocity after sublingual NTG administration (Dahl et al., ; Zuj et al., ). Likewise, others observed diminished MCA blood velocity but little change in regional CBF after intravenous infusions of sodium nitroglycerin (Iversen, Holm, Friberg, & Tfelt‐Hansen, ; White et al., ).…”

“…A major difference between these earlier studies in humans is that the former measured total flow, whereas the latter measured blood velocity, not accounting for conduit artery CSA. Previously, researchers in our laboratory (Coverdale et al, 2014) and others (Verbree et al, 2014) (Dahl et al, 1989;Zuj et al, 2012). Likewise, others observed diminished MCA blood velocity but little change in regional CBF after intravenous infusions of sodium nitroglycerin (Iversen, Holm, Friberg, & Tfelt-Hansen, 2008;White et al, 2000).…”

Vascular and Microvascular Dysfunction Induced by Microgravity and Its Analogs in Humans: Mechanisms and Countermeasures

“…Changes at the lower limb level are less homogenous. Vasodilation in response to nitroglycerin is unmodified after 25 days of horizontal bed rest (Bleeker et al, 2005b) or 56 days of HDBR (Zuj et al, 2012b), tends to increase after 49 days of HDBR (Platts et al, 2009), and increases after 28 days of unilateral lower limb suspension (Bleeker et al, 2005a) or 52 days of horizontal bed rest (Bleeker et al, 2005b). As for inflight reactivity of large arteries, endotheliumdependent and -independent vasodilation at brachial artery level is not substantially modified with long-term flight, while brachial diameter is unchanged (n = 13, measurements at d15, d60, d160; Lee et al, 2020).…”

Effects of Sex and Gender on Adaptation to Space: Cardiovascular Alterations

“…33 Different from men, cardiovascular responses to exogenous nitric oxide (sublingual nitroglycerin) are not altered by HDBR in women. 34 Prolonged bed rest may cause impairment of endotheliumdependent function at the microcirculation level in women. 35 The largest study to examine the responses of women to HDBR was the Women's International Space Simulation for Exploration (WISE)-2005 36 project that examined the effects of 60 days of HDBR in three groups of 8 women (control, exercise and nutrition).…”