RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats

1996 ◽  
Vol 271 (2) ◽  
pp. H602-H613 ◽  
Author(s):  
M. P. Kunert ◽  
J. F. Liard ◽  
D. J. Abraham
Keyword(s):  
Cardiac Output ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Experimental Models ◽  
Metabolic Demand ◽  
Flow Probe ◽  
Inositol Hexaphosphate ◽  
Control Value ◽  
Allosteric Effector

Tissue O2 delivery in excess of metabolic demand may be a factor in the development of high vascular resistance in experimental models of volume-expanded hypertension. This hypothesis was previously tested in rats with an exchange transfusion of red blood cells treated with inositol hexaphosphate or an intravenous infusion of RSR-4, allosteric effectors of hemoglobin. The binding of these drugs with hemoglobin effect a conformational change in the molecule, such that the affinity for O2 is reduced. However, in both preparations, the changes in vascular resistance could have been nonspecific. The present studies used intravenous infusions of RSR-13, which did not share some of the problematic characteristics of RSR-4 and inositol hexaphosphate. Conscious instrumented rats (an electromagnetic flow probe on ascending aorta or an iliac, mesenteric, or renal Doppler flow probe) were studied for 6 h after an RSR-13 infusion of 200 mg/kg in 15 min. This dose significantly increased arterial P50 (PO2 at which hemoglobin is 50% saturated) from 38 +/- 0.8 to 58 +/- 1.4 mmHg at 1 h after the start of the infusion. In the 3rd h cardiac output fell significantly from a control value of 358 +/- 33 to 243 +/- 24 ml.kg-1.min-1 and total peripheral resistance significantly increased from 0.31 +/- 0.03 to 0.43 +/- 0.04 mmHg.ml-1.kg.min. Cardiac output and P50 returned toward control over the next few hours. Neither cardiac output nor total peripheral resistance changed in the group of rats receiving vehicle alone. In a separate group of rats, iliac flow decreased significantly to 60% of control and iliac resistance increased to 160% of control. Iliac flow increased significantly in the group of rats that received vehicle only. Although the mechanism of these changes has not been established, these results suggest that a decreased O2 affinity leads to an increased total peripheral resistance and regional vascular resistance and support the hypothesis that O2 plays a role in the metabolic autoregulation of blood flow.

Angiotensin II: nitric oxide interaction and the distribution of blood flow

1993 ◽  
Vol 265 (6) ◽  
pp. R1276-R1283 ◽  
Author(s):  
D. H. Sigmon ◽  
W. H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Pressor Response ◽  
Peripheral Resistance ◽  
Conscious Rats

Nitric oxide (NO) contributes to the regulation of regional blood flow. Inhibition of NO synthesis increases blood pressure and vascular resistance. Using radioactive microspheres and the substrate antagonist N omega-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) to block NO synthesis, we tested the hypothesis that there is a significant interaction between the vasodilator NO and the vasoconstrictor angiotensin II, which regulates regional hemodynamics. Further, we investigated the influence of anesthesia on this interaction. L-NAME increased blood pressure, decreased cardiac output, and increased total peripheral resistance in both anesthetized and conscious rats. In anesthetized rats, L-NAME decreased blood flow to visceral organs (i.e. kidney, intestine, and lung) but had little effect on blood flow to the brain, heart, or hindlimb. Treating anesthetized rats with the angiotensin II receptor antagonist losartan (10 mg/kg) attenuated the decrease in cardiac output and the increase in total peripheral resistance without affecting the pressor response to L-NAME. Losartan also attenuated the visceral hemodynamic responses to L-NAME. In conscious rats, L-NAME decreased blood flow to all organ beds. Treating these rats with losartan only marginally attenuated the increase in total peripheral resistance to L-NAME without significantly affecting the pressor response or the decrease in cardiac output. Losartan had no effect on the regional hemodynamic responses to L-NAME. These data suggest that NO-mediated vascular relaxation is an important regulator of total peripheral and organ vascular resistance. (ABSTRACT TRUNCATED AT 250 WORDS)

Atrial extract: hemodynamics in Wistar-Kyoto and spontaneously hypertensive rats

1985 ◽  
Vol 249 (2) ◽  
pp. H265-H271 ◽  
Author(s):  
B. L. Pegram ◽  
M. B. Kardon ◽  
N. C. Trippodo ◽  
F. E. Cole ◽  
A. A. MacPhee
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Resistance Index ◽  
Organ Blood Flow ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Atrial Natriuretic

Partially purified low (LMW) and high-(HMW) molecular-weight atrial natriuretic extracts were administered intravenously (540 micrograms protein/kg) to conscious Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Both LMW and HMW atrial natriuretic extracts produced an immediate decrease in mean arterial pressure that reached maximum within 5 min and returned to control levels within 30 min. In both strains, cardiac output decreased approximately 14% following administration of LMW. Total peripheral resistance increased only in SHR. Organ blood flow was significantly decreased to skin, brain, heart, kidneys, and splanchnic organs of WKY and to skin, muscle, heart, and splanchnic organs of SHR following administration of LMW. Corresponding increases in organ vascular resistance index were observed in brain, heart, and splanchnic organs of WKY and in skin, heart, and splanchnic organs of SHR. To some extent, the changes in organ blood flow may be a reflection of the decrease in cardiac output induced by LMW. After administration of HMW, no significant changes were observed in cardiac output or total peripheral resistance, although they tended to decrease. Organ vascular resistance was decreased to skin, muscle, brain, and splanchnic organs of SHR. Little difference was observed between WKY and SHR responses to atrial natriuretic extracts. These data indicate that atrial natriuretic extracts have an effect on systemic and regional hemodynamics in conscious rats that differs markedly from those of vasodilators such as nitroglycerin or hydralazine.

Cardiovascular response to acute hypocapnia due to overbreathing

1964 ◽  
Vol 206 (5) ◽  
pp. 1025-1030 ◽  
Author(s):  
Robert C. Little ◽  
Charles W. Smith
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Artificial Respiration ◽  
Cardiovascular Response ◽  
Peripheral Resistance ◽  
Systemic Blood Pressure ◽  
Fixed Rate ◽  
Essential Change

Anesthetized dogs were maintained by artificial respiration at a fixed rate and depth. The composition of inspired CO2 was varied while O2 content was maintained at control levels. Cardiac output was measured by the indicator-dilution technique. Acute reduction of end-expiratory CO2 levels below the normal value caused a decrease in blood pressure, pulse pressure, stroke volume, and cardiac output, no essential change in heart rate and an increase in total peripheral resistance. Mean systemic blood pressure and net vascular resistance were less with hypocapnia than they were at the same cardiac output at normal CO2 levels. However, the over-all vascular resistance was greater with hypocapnia than it was in the same animal at normal CO2 levels and control output values. Analysis of these data leads to the conclusion that the hypocapnia produced by overbreathing causes some degree of net vasodilation. The hypotension associated with hyperventilation appears to result in these experiments from the drop in cardiac output and to a lesser degree the relatively less than normal compensatory increase in total peripheral resistance.

Time-Course of Vascular Resistance Changes in Mineralocorticoid Hypertension of Man

1981 ◽  
Vol 61 (s7) ◽  
pp. 97s-100s ◽  
Author(s):  
G. J. Wenting ◽  
A. J. Man in 'T Veld ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Vascular Resistance ◽  
Plasma Volume ◽  
High Resistance ◽  
Total Peripheral Resistance ◽  
Extracellular Volume ◽  
Peripheral Resistance ◽  
High Flow ◽  
Mean Blood Pressure

1. Repeated measurements of blood pressure, cardiac output (99mTc-labelled albumin dilution with single-probe precordial counting of radioactivity), plasma volume and extracellular volume were made in 20 subjects exposed to mineralocorticoid excess. Patients with aldosterone-producing adenoma (n = 14) were followed for 6 weeks during the recurrence of hypertension after spironolactone treatment had been stopped. Patients with adrenal insufficiency (n = 4) were followed for 6–9 weeks after treatment with dexamethasone (1 mg daily) and fludrocortisone (0.5 mg daily) was begun. Patients with severe orthostatic hypotension due to autonomic insufficiency (n = 2) were followed for 21 and 120 weeks while treated with fludrocortisone (0.25 mg daily). Measurements were made weekly during the first 6 weeks and with longer intervals thereafter. 2. All subjects showed increments of cardiac output, stroke volume, plasma volume and extracellular volume during the first 2 weeks with little or no increase in total peripheral resistance. Mean blood pressure rose from 104 ± 3 to 126 ± 5 mmHg (mean ± sem) (P < 0.001, n = 14) in that period in primary aldosteronism and from 85 ± 4 to 94 ± 6 mmHg (P > 0.05, n = 6) with fludrocortisone. 3. After 6 weeks hypertension was maintained by increased resistance in nine subjects, whereas cardiac output and plasma volume had returned towards normal (mean blood pressure at the end of the study 127 ± 4 mmHg). In the remainder hypertension was maintained by increased cardiac output and expanded plasma Volume for at least 6 weeks (mean blood pressure at the end of the study 131 ± 8 mmHg). The patients with the high-resistance pattern were older (56 ± 2 years) than the patients with the high-flow pattern (34 ± 2 years) (P < 0.01). 4. Mean blood pressure and extracellular fluid volume were positively correlated (r = 0.63, P < 0.001, n = 161). Cardiac output was positively correlated with plasma volume (r = 0.51, P < 0.001, n = 161), and total peripheral resistance was inversely correlated with the plasma volume/interstitial fluid volume ratio (r = 0.47, P < 0.001, n = 161). 5. The long duration of a high-flow state and the interindividual differences in progression of high-resistance hypertension argue against a cause-and-effect relation between flow and resistance through local metabolic factors (auto-regulation) as a hypertensive mechanism in sodium loading. The results are compatible with the view that fluid-shifts between the intravascular and extravascular compartments can influence the changes in cardiac output and resistance in early and sustained hypertension due to sodium overload. Cardiac output is increased when the proportion of fluid that is retained in the intravascular compartment is relatively high, and vascular resistance is increased when that proportion is relatively low.

Diastolic pressure and peripheral resistance during stellate ganglion stimulation

1963 ◽  
Vol 204 (1) ◽  
pp. 71-72 ◽  
Author(s):  
Edward D. Freis ◽  
Jay N. Cohn ◽  
Thomas E. Liptak ◽  
Aristide G. B. Kovach
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Total Peripheral Resistance ◽  
Diastolic Pressure ◽  
Stellate Ganglion ◽  
Peripheral Resistance ◽  
Resistance Vessels ◽  
Left Stellate Ganglion ◽  
Increased Blood Flow

The mechanism of the diastolic pressure elevation occurring during left stellate ganglion stimulation was investigated. The cardiac output rose considerably, the heart rate remained essentially unchanged, and the total peripheral resistance fell moderately. The diastolic rise appeared to be due to increased blood flow rather than to any active changes in resistance vessels.

scholarly journals Elevated Blood Pressure in Adolescence Is Attributable to a Combination of Elevated Cardiac Output and Total Peripheral Resistance

Hypertension ◽  
2018 ◽  
Vol 72 (5) ◽  
pp. 1103-1108 ◽  
Author(s):  
Chloe Park ◽  
Abigail Fraser ◽  
Laura D. Howe ◽  
Siana Jones ◽  
George Davey Smith ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Elevated Blood Pressure ◽  
Elevated Blood

Long-term hemodynamic actions of atrial natriuretic factor (99-126) in conscious sheep

1988 ◽  
Vol 254 (4) ◽  
pp. H811-H815 ◽  
Author(s):  
D. G. Parkes ◽  
J. P. Coghlan ◽  
J. G. McDougall ◽  
B. A. Scoggins
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Stroke Volume ◽  
Blood Volume ◽  
Total Peripheral Resistance ◽  
Atrial Natriuretic Factor ◽  
Peripheral Resistance ◽  
Natriuretic Factor ◽  
Atrial Natriuretic

The hemodynamic and metabolic effects of long-term (5 day) infusion of human atrial natriuretic factor (ANF) were examined in conscious chronically instrumented sheep. Infusion of ANF at 20 micrograms/h, a rate below the threshold for an acute natriuretic effect, decreased blood pressure by 9 +/- 1 mmHg on day 5, associated with a fall in calculated total peripheral resistance. On day 1, ANF reduced cardiac output, stroke volume, and blood volume, effects that were associated with an increase in heart rate and calculated total peripheral resistance and a small decrease in blood pressure. On days 4 and 5 there was a small increase in urine volume and sodium excretion. On day 5 an increase in water intake and body weight was observed. No change was seen in plasma concentrations of renin, arginine vasopressin, glucose, adrenocorticotropic hormone, or protein. This study suggests that the short-term hypotensive effect of ANF results from a reduction in cardiac output associated with a fall in both stroke volume and effective blood volume. However, after 5 days of infusion, ANF lowers blood pressure via a reduction in total peripheral resistance.

Plotting cardiac output versus total peripheral resistance

1981 ◽  
Vol 9 (2) ◽  
pp. 129-130
Author(s):  
Heinz Mrochen ◽  
Ullrich Hieronymi ◽  
Werner Kuckelt
Keyword(s):  
Cardiac Output ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance

In vivo characterization of vasocontractile activities in erythrocytes

1983 ◽  
Vol 58 (3) ◽  
pp. 356-361 ◽  
Author(s):  
Michael P. McIlhany ◽  
Lydia M. Johns ◽  
Thomas Leipzig ◽  
Nicholas J. Patronas ◽  
Frederick D. Brown ◽  
...  
Keyword(s):  
Vascular Resistance ◽  
Peripheral Resistance ◽  
Content Type ◽  
Control Value ◽  
Arterial Blood ◽  
Anesthetized Dogs ◽  
Chronic Cerebral Vasospasm ◽  
In Vivo Characterization

✓ Partially purified protein from washed and artificially hemolyzed erythrocytes, known to cause significant contractions of isolated canine cerebral vessels in vitro, was injected into the cisterna magna of intact anesthetized dogs. Cerebral blood flow, measured by the xenon-133 washout technique, decreased from a control value of 49.5 ± 1.17 ml/100 gm/min to an experimental value of 34.1 ± 1.65 ml/100 gm/min at 2 hours. Cerebral vascular resistance rose from a control value of 2.05 ± 0.17 PRU (peripheral resistance units) to an experimental value of 2.91 ± 0.25 PRU at 2 hours. Mean arterial blood pressure, heart rate, intracranial pressure, and cerebral perfusion pressure remained stable. Cardiac output also fell significantly (in 2-hour control animals it was 2.89 ± 0.37 liter/min, and in 2-hour experimental animals 1.43 ± 0.13 liter/min) and peripheral vascular resistance rose. These changes were evident by 10 minutes after the cisternal injection of the hemolysate protein, and remained for the duration of the 2-hour monitoring period. Serial vertebrobasilar angiograms demonstrated marked narrowing of the intracranial basilar artery when compared to control values. The narrowing persisted for several days in most animals, and tended to increase with time. Relaxation occurred by the 10th through the 14th day. The authors conclude that this experimental preparation may be a useful model for both in vitro and in vivo investigation of chronic cerebral vasospasm.

Effect of sympathetic blockade on diurnal variation of hemodynamic patterns

1989 ◽  
Vol 256 (3) ◽  
pp. R778-R785 ◽  
Author(s):  
M. I. Talan ◽  
B. T. Engel
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Stroke Volume ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Base Line ◽  
Sympathetic Blockade ◽  
Selective Blockade ◽  
Arterial Blood

Heart rate, stroke volume, and intra-arterial blood pressure were monitored continuously in each of four monkeys, 18 consecutive h/day for several weeks. The mean heart rate, stroke volume, cardiac output, systolic and diastolic blood pressure, and total peripheral resistance were calculated for each minute and reduced to hourly means. After base-line data were collected for approximately 20 days, observation was continued for equal periods of time under conditions of alpha-sympathetic blockade, beta-sympathetic blockade, and double sympathetic blockade. This was achieved by intra-arterial infusion of prazosin, atenolol, or a combination of both in concentration sufficient for at least 75% reduction of response to injection of agonists. The results confirmed previous findings of a diurnal pattern characterized by a fall in cardiac output and a rise in total peripheral resistance throughout the night. This pattern was not eliminated by selective blockade, of alpha- or beta-sympathetic receptors or by double sympathetic blockade; in fact, it was exacerbated by sympathetic blockade, indicating that the sympathetic nervous system attenuates these events. Because these findings indicate that blood volume redistribution is probably not the mechanism mediating the observed effects, we have hypothesized that a diurnal loss in plasma volume may mediate the fall in cardiac output and that the rise in total peripheral resistance reflects a homeostatic regulation of arterial pressure.

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