scholarly journals Essential Role of Hemoglobin βCys93 in Cardiovascular Physiology

Physiology ◽  
2020 ◽  
Vol 35 (4) ◽  
pp. 234-243 ◽  
Author(s):  
Richard T. Premont ◽  
Jonathan S. Stamler
Keyword(s):  
Blood Flow ◽  
Reactive Hyperemia ◽  
Tissue Hypoxia ◽  
Microvascular Blood Flow ◽  
Cardiovascular Physiology ◽  
Transient Ischemia ◽  
Microcirculatory Blood Flow ◽  
Physiological Basis ◽  
Hb S

The supply of oxygen to tissues is controlled by microcirculatory blood flow. One of the more surprising discoveries in cardiovascular physiology is the critical dependence of microcirculatory blood flow on a single conserved cysteine within the β-subunit (βCys93) of hemoglobin (Hb). βCys93 is the primary site of Hb S-nitrosylation [i.e., S-nitrosothiol (SNO) formation to produce S-nitrosohemoglobin (SNO-Hb)]. Notably, S-nitrosylation of βCys93 by NO is favored in the oxygenated conformation of Hb, and deoxygenated Hb releases SNO from βCys93. Since SNOs are vasodilatory, this mechanism provides a physiological basis for how tissue hypoxia increases microcirculatory blood flow (hypoxic autoregulation of blood flow). Mice expressing βCys93A mutant Hb (C93A) have been applied to understand the role of βCys93, and RBCs more generally, in cardiovascular physiology. Notably, C93A mice are unable to effect hypoxic autoregulation of blood flow and exhibit widespread tissue hypoxia. Moreover, reactive hyperemia (augmentation of blood flow following transient ischemia) is markedly impaired. C93A mice display multiple compensations to preserve RBC vasodilation and overcome tissue hypoxia, including shifting SNOs to other thiols on adult and fetal Hbs and elsewhere in RBCs, and growing new blood vessels. However, compensatory vasodilation in C93A mice is uncoupled from hypoxic control, both peripherally (e.g., predisposing to ischemic injury) and centrally (e.g., impairing hypoxic drive to breathe). Altogether, physiological studies utilizing C93A mice are confirming the allosterically controlled role of SNO-Hb in microvascular blood flow, uncovering essential roles for RBC-mediated vasodilation in cardiovascular physiology and revealing new roles for RBCs in cardiovascular disease.

Role of adenosine in postprandial and reactive hyperemia in canine jejunum

1992 ◽  
Vol 263 (4) ◽  
pp. G487-G493 ◽  
Author(s):  
D. R. Sawmiller ◽  
C. C. Chou
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Adenosine Deaminase ◽  
Reactive Hyperemia ◽  
Concentration Difference ◽  
Adenosine Concentration ◽  
Anesthetized Dogs ◽  
Series Of Experiments ◽  
Increased Blood Flow

The role of adenosine in postprandial jejunal hyperemia was investigated by determining the effect of placement of predigested food into the jejunal lumen on blood flow and oxygen consumption before and during intra-arterial infusion of dipyridamole (1.5 microM arterial concn) or adenosine deaminase (9 U/ml arterial concn) in anesthetized dogs. Neither drug significantly altered resting jejunal blood flow and oxygen consumption. Before dipyridamole or deaminase, food placement increased blood flow by 30-36%, 26-42%, and 21-46%, and oxygen consumption by 13-22%, 21-22%, and 26-29%, during 0- to 3-, 4- to 7-, and 8- to 11-min placement periods, respectively. Adenosine deaminase abolished the entire 11-min hyperemia, whereas dipyridamole significantly enhanced the initial 7-min hyperemia (45-49%). Both drugs abolished the initial 7-min food-induced increase in oxygen consumption. Dipyridamole attenuated (14%), whereas deaminase did not alter (28%), the increased oxygen consumption that occurred at 8-11 min. Adenosine deaminase also prevented the food-induced increase in venoarterial adenosine concentration difference. In separate series of experiments, luminal placement of food significantly increased jejunal lymphatic adenosine concentration and release. Also, reactive hyperemia was accompanied by an increase in venous adenosine concentration and release. This study provides further evidence to support the thesis that adenosine plays a role in postprandial and reactive hyperemia in the canine jejunum.

Intracoronary adenosine enhances myocardial reactive hyperemia after brief coronary occlusion

1985 ◽  
Vol 248 (6) ◽  
pp. H812-H817
Author(s):  
D. Saito ◽  
T. Hyodo ◽  
K. Takeda ◽  
Y. Abe ◽  
H. Tani ◽  
...  
Keyword(s):  
Blood Flow ◽  
Left Atrium ◽  
Coronary Occlusion ◽  
Reactive Hyperemia ◽  
Control Level ◽  
Direct Effects ◽  
Intracoronary Infusion ◽  
Hyperemic Flow ◽  
Hyperemic Response

Adenosine is a prime candidate for the role of mediator between myocardial metabolic state and coronary blood flow. However, there are few reports concerning the direct effects of exogenously added adenosine on coronary autoregulation. The present investigation in the open-chest dog studied the effects of a threshold dose of intracoronary adenosine infusion on reactive hyperemia following brief coronary occlusions. The infused dose did not increase nonocclusive flow by greater than 10%. Adenosine enhanced total hyperemic flow at all occlusions tested (5, 10, 15, 20, and 30 s). Aminophylline pretreatment reduced reactive hyperemia below the control level even in the presence of an intracoronary infusion of adenosine. Adenosine injected into the left atrium and intracoronarily infused papaverine did not affect hyperemic response to 5- and 15-s coronary occlusions. The results suggest that a minimum dose of exogenously added adenosine enhances myocardial reactive hyperemia, possibly by potentiating the effects of endogenous adenosine released during ischemia.

scholarly journals Role of C-Peptide in the Regulation of Microvascular Blood Flow

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
T. Forst ◽  
T. Kunt ◽  
B. Wilhelm ◽  
M. M. Weber ◽  
A. Pfützner
Keyword(s):  
Blood Flow ◽  
Beta Cell ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Microvascular Blood Flow ◽  
Diabetic Patients ◽  
C Peptide ◽  
Glucose Levels ◽  
Peptide Secretion

During the recent years, the role of C-peptide, released from the pancreatic beta cell, in regulating microvascular blood flow, has received increasing attention. In type 1 diabetic patients, intravenous application of C-peptide in physiological concentrations was shown to increase microvascular blood flow, and to improve microvascular endothelial function and the endothelial release of NO. C-peptide was shown to impact microvascular blood flow by several interactive pathways, like stimulatingNa+K+ATPase or the endothelial release of NO. There is increasing evidence, that in patients with declining beta cell function, the lack of C-peptide secretion might play a putative role in the development of microvascular blood flow abnormalities, which go beyond the effects of declining insulin secretion or increased blood glucose levels.

Inhibition of vascular ATP-sensitive K+channels does not affect reactive hyperemia in human forearm

2003 ◽  
Vol 284 (2) ◽  
pp. H711-H718 ◽  
Author(s):  
H. M. Omar Farouque ◽  
Ian T. Meredith
Keyword(s):  
Blood Flow ◽  
Adaptive Response ◽  
Healthy Subjects ◽  
Forearm Blood Flow ◽  
Reactive Hyperemia ◽  
Venous Occlusion ◽  
Channel Inhibition ◽  
Human Forearm ◽  
Hyperemic Response

The extent to which ATP-sensitive K+ channels contribute to reactive hyperemia in humans is unresolved. We examined the role of ATP-sensitive K+channels in regulating reactive hyperemia induced by 5 min of forearm ischemia. Thirty-one healthy subjects had forearm blood flow measured with venous occlusion plethysmography. Reactive hyperemia could be reproducibly induced ( n = 9). The contribution of vascular ATP-sensitive K+ channels to reactive hyperemia was determined by measuring forearm blood flow before and during brachial artery infusion of glibenclamide, an ATP-sensitive K+ channel inhibitor ( n = 12). To document ATP-sensitive K+ channel inhibition with glibenclamide, coinfusion with diazoxide, an ATP-sensitive K+ channel opener, was undertaken ( n = 10). Glibenclamide did not significantly alter resting forearm blood flow or the initial and sustained phases of reactive hyperemia. However, glibenclamide attenuated the hyperemic response induced by diazoxide. These data suggest that ATP-sensitive K+ channels do not play an important role in controlling forearm reactive hyperemia and that other mechanisms are active in this adaptive response.

Role of chemical factors in regulation of flow through kidney, hindlimb, and heart

1965 ◽  
Vol 208 (5) ◽  
pp. 813-824 ◽  
Author(s):  
J. B. Scott ◽  
R. M. Daugherty ◽  
J. M. Dabney ◽  
F. J. Haddy
Keyword(s):  
Blood Flow ◽  
Metabolic Rate ◽  
Flow Resistance ◽  
Reactive Hyperemia ◽  
Venous Outflow ◽  
Chemical Factors ◽  
Study Support ◽  
Dog Blood ◽  
Flow Through

In the anesthetized dog, blood flow or metabolic rate was varied in kidney, hindlimb, or heart (experimental organ) while simultaneously diverting a portion of the venous outflow through forelimb or kidney (bioassay organ). The resistance to blood flow through the experimental organ gradually rose in the first few minutes following a large increase in flow and gradually fell following a large decrease in flow. Resistance to blood flow through an experimental organ (hindlimb) fell following increase in metabolic rate. In each case, bioassay organ resistance changed in the same direction when the assay organ was the forelimb and in the opposite direction when the assay organ was the kidney. These findings suggest that active hyperemia, reactive hyperemia, and autoregulation of blood flow result, at least in part, from alteration in the chemical environment of the blood vessels. Other findings in this study support the possibility that adenosine triphosphate contributes to the change in environment.

A restrospective perspective

2005 ◽  
Vol 98 (2) ◽  
pp. 762-763 ◽  
Author(s):  
John Gamble
Keyword(s):  
Blood Flow ◽  
Adrenergic Receptors ◽  
Reactive Hyperemia ◽  
Venous Occlusion ◽  
Venous Occlusion Plethysmography ◽  
Limb Blood Flow ◽  
Major Area ◽  
Vasoactive Factors ◽  
Health And Disease

Venous occlusion plethysmography is a simple but elegant technique that has contributed to almost every major area of vascular biology in humans. The general principles of plethysmography were appreciated by the late 1800s, and the application of these principles to measure limb blood flow occurred in the early 1900s. Plethysmography has been instrumental in studying the role of the autonomic nervous system in regulating limb blood flow in humans and important in studying the vasodilator responses to exercise, reactive hyperemia, body heating, and mental stress. It has also been the technique of choice to study how human blood vessels respond to a variety of exogenously administered vasodilators and vasoconstrictors, especially those that act on various autonomic and adrenergic receptors. In recent years, plethysmography has been exploited to study the role of the vascular endothelium in health and disease. Venous occlusion plethysmography is likely to continue to play an important role as investigators seek to understand the physiological significance of newly identified vasoactive factors and how genetic polymorphisms affect the cardiovascular system in humans.

Role of nitric oxide in vasodilator response induced by salbutamol in rat diaphragmatic microcirculation

1997 ◽  
Vol 272 (5) ◽  
pp. H2173-H2179 ◽  
Author(s):  
H. Y. Chang
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cyclic Amp ◽  
Laser Doppler Flowmetry ◽  
Ringer Solution ◽  
Laser Doppler ◽  
Microvascular Blood Flow ◽  
Doppler Flowmetry ◽  
Vasodilator Response

To determine the contribution of nitric oxide (NO) to the vasodilator response induced by salbutamol in diaphragmatic microcirculation, we studied a diaphragmatic preparation in anesthetized rats. With bicarbonate-buffered Ringer solution continuously suffusing the diaphragm, laser-Doppler flowmetry was used to record microvascular blood flow (QLDF). The drugs were applied to the surface of the diaphragm. Salbutamol (3.2 x 10(-7)-10(-4) M), isoproterenol (3.2 x 10(-8)-3.2 x 10(-6) M), and forskolin (3.2 x 10(-7)-10(-5) M) each elicited a concentration-dependent increase in QLDF. The vasodilator response induced by salbutamol (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was attenuated by a 15-min suffusion of N omega-nitro-L-arginine (L-NNA, 10(-4) M), and pretreatment with L-arginine (10(-2) M) could restore salbutamol-induced vasodilator responses. Salbutamol-induced vasodilation was also abolished by propranolol (10(-5) M). Similarly, the vasodilator response elicited by isoproterenol (3.2 x 10(-8), 10(-7), and 3.2 x 10(-7) M) and forskolin (3.2 x 10(-7), 10(-6), and 3.2 x 10(-6) M) was inhibited by L-NNA (10(-4) M). In contrast, the vasodilator response induced by adenosine (10(-6), 10(-5), and 10(-4) M) was not affected by L-NNA (10(-4) M). These data indicate that in rat diaphragmatic microcirculation salbutamol-induced vasodilation may be partly mediated by beta-adrenoceptors on the endothelium. Moreover, these data suggest that an elevation of cyclic AMP in the endothelium may cause release of NO.

Failure to abolish reactive hyperemia by indomethacin in denervated kidneys of rabbits

1977 ◽  
Vol 233 (2) ◽  
pp. F89-F93
Author(s):  
C. Aizawa ◽  
N. Honda
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Reactive Hyperemia ◽  
Fractional Flow ◽  
Outer Cortex ◽  
Cortical Blood Flow ◽  
Before And After ◽  
Inner Cortex ◽  
Postocclusive Reactive Hyperemia

The effect of indomethacin (10 mg/kg) on the distribution of cortical blood flow during postocclusive reactive hyperemia was evaluated in denervated kidneys of anesthetized rabbits by the radioactive microsphere technique. Renal denervation caused a slight but not significant increase in renal blood flow with no remarkable alteration in the distribution of cortical blood flow. After release of 1-min occlusion of the renal artery, hyperemic responses developed with a fractional flow redistribution toward the inner cortex. The absolute perfusion rate increased in the inner cortex but did not significantly change in the outer cortex. Indomethacin produced a decrease in renal blood flow despite elevated blood pressure. Even in the indomethacin-treated animals, postocclusive reactive hyperemia appeared concomitantly with the fractional flow redistribution to the inner cortex. The percentage repayment by reactive hyperemia of ischemia during the artery clamping was not significantly different before and after indomethacin administration. The findings indicate that indomethacin did not significantly affect the postocclusive vascular response in denervated kidneys of rabbits, thereby giving evidence against the role of prostaglandins as mediators of reactive hyperemia.

Venoarterial CO2 difference during regional ischemic or hypoxic hypoxia

2000 ◽  
Vol 89 (4) ◽  
pp. 1317-1321 ◽  
Author(s):  
Benoit Vallet ◽  
Jean-Louis Teboul ◽  
Stephen Cain ◽  
Scott Curtis
Keyword(s):  
Blood Flow ◽  
Tissue Hypoxia ◽  
Hypoxic Hypoxia ◽  
Systemic Hemodynamics ◽  
Membrane Oxygenator ◽  
Normal Range ◽  
Ischemic Hypoxia ◽  
Controlled Flow

To test the role of blood flow in tissue hypoxia-related increased veno-arterial Pco 2difference (ΔPco 2), we decreased O2 delivery (D˙o 2) by either decreasing flow [ischemic hypoxia (IH)] or arterial Po 2 [hypoxic hypoxia (HH)] in an in situ, vascularly isolated, innervated dog hindlimb perfused with a pump-membrane oxygenator system. Twelve anesthetized and ventilated dogs were studied, with systemic hemodynamics maintained within normal range. In the IH group ( n = 6), hindlimbD˙o 2 was progressively lowered every 15 min by decreasing pump-controlled flow from 60 to 10 ml · kg−1 · min−1, with arterial Po 2 constant at 100 Torr. In the HH group ( n = 6), hindlimbD˙o 2 was progressively lowered every 15 min by decreasing Po 2 from 100 to 15 Torr, when flow was constant at 60 ml · kg−1 · min−1. LimbD˙o 2, O2 uptake (V˙o 2), and ΔPco 2 were obtained every 15 min. Below the criticalD˙o 2,V˙o 2 decreased, indicating dysoxia, and O2 extraction ratio (V˙o 2/D˙o 2) rose continuously and similarly in both groups, reaching a maximal value of ∼90%. ΔPco 2 significantly increased in IH but never differed from baseline in HH. We conclude that absence of increased ΔPco 2 does not preclude the presence of tissue dysoxia and that decreased flow is a major determinant in increased ΔPco 2.

THE ROLE OF ARTERIOVENOUS ANASTOMOSES IN COLD-INDUCED VASODILATION, REWARMING, AND REACTIVE HYPEREMIA AS DETERMINED BY 24Na CLEARANCE

1967 ◽  
Vol 45 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Merrill A. Edwards
Keyword(s):  
Blood Flow ◽  
Reactive Hyperemia ◽  
Arteriovenous Anastomoses ◽  
Total Flow ◽  
Initial Flow

The rate of removal of 24Na from a deposit in the rabbit's foot was used to determine the degree of involvement of arteriovenous anastomoses in the blood flow of cold-induced vasodilation, in the rewarming following intense vasoconstriction, and in reactive hyperemia. The results indicate that in the first two cases the total flow is through the arteriovenous anastomoses. In reactive hyperemia an initial flow which is partly capillary and partly through the anastomoses gives way to a flow which is entirely through the anastomoses.

Sign in / Sign up

Export Citation Format

Share Document