Disease relevance of EVC2

• A novel heterozygous deletion in the EVC2 gene causes Weyers acrofacial dysostosis [1].
• LBN rats bearing acute myelocytic leukemia (AML) were treated with 100 mg Ara-C/kg q.8 h six times beginning on day 0 and on other days in sequence (0,1 through 0,12) [2].
• LBNP caused less reduction in FBF in refractory ascites patients than in both preascitic patients and controls (P < 0.01) [3].
• Attenuated LBNP responses occurred only in advanced cirrhosis, without apparent interaction with endogenous ANG II [3].
• Seven of 13 subjects had presyncope during LBNP, all associated with a sudden drop in BP (29 +/- 9%) [4].

Psychiatry related information on EVC2

• A beneficial effect of the LBNP sessions on simple tests involving the visual-motor coordination and attention faculties can only be regarded as a mere trend [5].
• Psychomotor testing showed a significant slowing of reaction time with LBNP, but only for the easiest component of a complex task, while saccadic latencies were found to be shortened following LBNP exposure [6].

High impact information on EVC2

• To determine whether epinephrine facilitates neurogenic vasoconstriction in humans, we contrasted forearm vasoconstrictor responses to a reflex stimulus (lower body negative pressure [LBNP]) and to intraarterial NE before, during, and 30 min after infusion of epinephrine (50 ng/min) or isoproterenol (10 or 25 ng/min) into a brachial artery [7].
• The ratio of vasoconstrictor responses to LBNP/NE was used as an index of neural release of the neurotransmitter NE [7].
• We reasoned that if prejunctional stimulation of beta receptors by epinephrine and isoproterenol had functional significance, the vasoconstrictor response to LBNP would be potentiated in comparison to the response to NE (postjunctional mechanism) [7].
• In contrast, 30 min after isoproterenol the vasoconstrictor responses to LBNP and NE were the same as before isoproterenol [7].
• METHODS: Forearm blood flow (FBF) responses to lower body negative pressure (LBNP) and to subsystemic, intrabrachial infusions of losartan, an angiotensin II type 1 (AT(1)) receptor antagonist, norepinephrine, and ANG II were measured using venous occlusion plethysmography [3].

Chemical compound and disease context of EVC2

• After propranolol, there was a significant reduction in the increase in FVR induced by -40 mm Hg LBNP in normal subjects (+107 +/- 5 vs +129 +/- 15 mm Hg/ml/sec, p less than .05) but not in patients with hypertension [8].
• In patients with congestive heart failure neither nitroglycerin nor LBNP changed forearm vascular resistance [9].
• In a separate group of hypertensive patients with left ventricular hypertrophy, exogenous infusion of ANF induced an increase in venous irANF plasma levels of the same magnitude of the decrease evoked by LBNP and significantly reduced forearm vascular resistance [10].
• After furosemide-induced volume reduction associated with 1.6 +/- 0.2 kg weight loss and approximately 7% blood volume reduction, five of them developed vasodilatory presyncope after 17 +/- 5 min of LBNP [11].
• It was concluded that the stimuli for exercise hyperemia during moderate and heavy, but not mild, handgrip exercise intensities, diminish the vasoconstrictor effects of LBNP [12].

Biological context of EVC2

• Pressor and heart rate responses to handgrip also were unaffected by LBNP [13].
• LBNP alone (cardiac reflex) did not alter blood pressure or heart rate but decreased central venous pressure by 2.5 +/- 0.1 mm Hg (mean +/- SEM, p less than 0.05) and increased MSNA by 92 +/- 22% over the control value [13].
• In patients with vasovagal syncope, during the application of -10 mm Hg LBNP, forearm vascular resistance decreased by 0.7 +/- 11.6 U versus an increase of 8.3 +/- 6.2 U in control subjects (P = .002) [14].
• Increases of sympathetic nerve activity, however, were significantly greater in borderline hypertensive than in normotensive subjects at each level of LBNP, indicating an augmented gain of the cardiopulmonary baroreflex [15].
• LBNP produced similar decreases in central venous pressure in all groups before and after drug administration [16].

Anatomical context of EVC2

• In conclusion, this study provides direct evidence in humans that nonhypotensive LBNP does not augment muscle sympathetic outflow during static handgrip and challenges the concept of an important interaction between cardiac baroreceptor and exercise pressor reflexes during this form of exercise [13].
• Noninvasive measures of cardiac output, heart rate, blood pressure, forearm flow and leg volume during lower body negative pressure (LBNP) showed that patients had less lower extremity pooling of blood and had lower forearm conductance [17].
• In 11 healthy humans, we recorded muscle sympathetic nerve activity (MSNA) with microelectrodes (peroneal nerve), as well as blood flow in the forearm and calf (venous occlusion plethysmography) at baseline and during graded LBNP [18].
• The findings that left atrial diameter decreased and plasma norepinephrine concentration increased during LBNP -10 mm Hg suggest that the sympathetic nervous system is sensitive to changes in atrial receptor activity [19].
• We tested this hypothesis directly by making intraneural measurements of skeletal muscle sympathetic nerve activity (MSNA; peroneal microneurography) in groups of young (23+/-1 years; n=11) and older (64+/-1 years; n=12) healthy adult men during progressive hypovolemia produced by graded (-5 to -40 mm Hg) lower body negative pressure (LBNP) [20].

Associations of EVC2 with chemical compounds

• Forearm blood flow (FABF; mL x dL forearm(-1) x min(-1)) responses to LBNP (-20 cm H2O) and increasing increments of norepinephrine (60, 120, and 240 pmol/min) were compared when coinfused with placebo and perindoprilat (5 nmol/mL) [21].
• Thus, propranolol significantly (p less than 0.05) reduced responses to LBNP at -40 mm Hg [22].
• Central venous pressure was held at control levels by LBNP during phenylephrine and saline infusion during nitroprusside [15].
• In contrast, administration of hemodynamically similar doses of nitroprusside resulted in an attenuation of MSNA responses to LBNP-10 [23].
• In normal subjects, LBNP increased but nitroglycerin did not change forearm vascular resistance [9].

Other interactions of EVC2

• Affected individuals with mutations in EVC and EVC2 have the typical spectrum of features and are phenotypically indistinguishable [24].

Analytical, diagnostic and therapeutic context of EVC2

• We measured pulmonary capillary wedge (PCW) pressure (Swan-Ganz catheter), LVEDV (two-dimensional echocardiography), and cardiac output (C2H2 rebreathing) during lower body negative pressure (LBNP, -15 and -30 mm Hg) and rapid saline infusion (15 and 30 ml/kg) in seven athletes and six controls (VO2max, 68 +/- 7 and 41 +/- 4 ml/kg/min) [25].
• To further test this concept in humans, we measured sympathetic nerve discharge with intraneural microelectrodes while we used static handgrip to activate the exercise pressor reflex and nonhypotensive lower-body negative pressure (LBNP) to selectively unload the cardiac baroreflex [13].
• Despite high baseline values for FVR, patients with LVD developed vasoconstriction during intra-arterial infusions of norepinephrine, thereby excluding a nonspecific depression of vascular reactivity as the mechanism for abnormal responses to LBNP in patients with LVD [26].
• CONCLUSIONS: This is the first study showing that brief cold stress, tolerated well in normal circulatory conditions, can provoke sudden sympathoinhibition and hypotension when applied during decreased cardiac output induced by LBNP or hemodialysis [27].
• (2) In heart transplant recipients, a small increase in MSNA during mild LBNP was dependent on a decrease in arterial pressure, but in normal subjects, a similar increase in MSNA occurred in the absence of any detectable decrease in the aortic pressure stimulus to the sinoaortic baroreceptors [28].

References