Abstract MP19: Endogenous 5-hydroxytryptamine May Regulate Skeletal Muscle Vascular Resistance In Normal Healthy Rats

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Gregory D Fink
Keyword(s):  
Skeletal Muscle ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Recovery Period ◽  
Peripheral Resistance ◽  
Cardiovascular Effects ◽  
Wild Type ◽  
Sprague Dawley ◽  
Vascular Beds ◽  
Hemodynamic Measurements

Infusing low doses of 5-hydroxytryptamine (5-HT) into normal rats causes chronic (weeks to months) hypotension and a fall in total peripheral resistance. These effects are mediated by activation of 5-HT 7 receptors. Therefore, we generated 5-HT 7 receptor knockout rats (5-HT 7 KO) to explore possible cardiovascular effects of 5-HT 7 receptors under normal and pathophysiological conditions. We previously reported that healthy 5-HT 7 KO rats have normal blood pressure and total peripheral resistance at rest. This suggested that 5-HT 7 receptors plays no role in cardiovascular regulation under normal conditions. But total peripheral resistance is determined by multiple vascular beds that differ in their sensitivity to 5-HT. Others have indicated that 5-HT 7 receptors in the skeletal muscle vasculature are particularly sensitive to the effects of 5-HT. Therefore, we hypothesized that 5-HT 7 KO rats would show both reduced responsiveness to exogenous 5-HT and increased resting skeletal muscle vascular resistance. Experiments were performed in isoflurane-anesthetized, male Sprague-Dawley (SD) (n=6), 5-HT 7 wild-type (5-HT 7 WT) (n=5) and 5-HT 7 KO (n=6) rats at 7-8 months of age. Arterial pressure was measured with an aortic catheter. Blood flow to the hindquarters (mostly skeletal muscle) was measured with transit-time, ultrasound flowmetry. After 10 minutes of baseline hemodynamic measurements were obtained, 5-HT was infused iv at a rate of 25 μg/kg/min for 15 minutes, followed by a 15-minute recovery period. As expected, 5-HT 7 KO rats did not show a significant fall in hindquarter vascular resistance (HQVR) during 5-HT infusion, while SD and 5-HT 7 WT did. More importantly, HQVR at baseline was significantly (p < 0.05) higher in 5-HT 7 KO rats (16.0 ± 2.0 mmHg/ml/min) than in 5-HT 7 WT rats (10.9 ± 0.06 mmHg/ml/min) or SD rats (7.0 ± 0.03 mmHg/ml/min). These results support our hypothesis that in healthy (albeit anesthetized) rats, 5-HT 7 receptors reduce skeletal muscle vascular resistance.

scholarly journals Reduction in Hindquarter Vascular Resistance Supports 5-HT7 Receptor Mediated Hypotension

2021 ◽  
Vol 12 ◽  
Author(s):  
Bridget M. Seitz ◽  
Stephanie W. Watts ◽  
Gregory D. Fink
Keyword(s):  
Skeletal Muscle ◽  
Vascular Resistance ◽  
Low Dose ◽  
Peripheral Resistance ◽  
Cardiovascular Effects ◽  
Hemodynamic Response ◽  
Receptor Activation ◽  
Male Rats ◽  
Vascular Beds ◽  
Vascular Catheters

The 5-HT7 receptor is the primary mediator of both the acute (&lt;hours) and chronic (day-week) decreases in mean arterial pressure (MAP) during low dose 5-HT infusion in rats. Previous data show the hypotensive response during chronic 5-HT infusion is due to a decrease total peripheral resistance (TPR) and specifically splanchnic vascular resistance. We hypothesized that changes in vascular resistance in both the splanchnic and skeletal muscle vascular beds are critical to the cardiovascular effects mediated by the 5-HT7 receptor. Systemic and regional hemodynamic data were collected in conscious and anesthetized male rats using radiotelemetry, vascular catheters and transit-time flowmetry. Reversible antagonism of the 5-HT7 receptor was achieved with the selective antagonist SB269970 (33 μg/kg, iv). From the very beginning and throughout the duration (up to 5 days) of a low dose (25 μg/kg) infusion of 5-HT, TPR, and MAP were decreased while cardiac output (CO) was increased. In a separate group of rats, the contribution of the 5-HT7 receptor to the regional hemodynamic response was tested during 5-HT-induced hypertension. The decrease in MAP after 24 h of 5-HT (saline 83 ± 3 vs. 5-HT 72 ± 3 mmHg) was associated with a significant decrease in skeletal muscle vascular resistance (saline 6 ± 0.2 vs. 5-HT 4 ± 0.4 mmHg/min/mL) while splanchnic vascular resistance was similar in 5-HT and saline-treated rats. When SB269970 was administered acutely, MAP and skeletal muscle vascular resistance rapidly increased, whereas splanchnic resistance was unaffected. Our work suggests the most prominent regional hemodynamic response to 5-HT7 receptor activation paralleling the fall in MAP is a decrease in skeletal muscle vascular resistance.

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.

Reflex effects of thoracic aorta wall stretch on regional vascular resistance

1978 ◽  
Vol 56 (3) ◽  
pp. 390-394
Author(s):  
Peter M. Szeto ◽  
Franco Lioy
Keyword(s):  
Arterial Pressure ◽  
Thoracic Aorta ◽  
Vascular Resistance ◽  
Carotid Arteries ◽  
Peripheral Resistance ◽  
Adrenergic Blockade ◽  
Vascular Responses ◽  
Regional Vascular Resistance ◽  
Vascular Beds ◽  
Intact Limb

In anesthetized, vagotomized cats with both carotid arteries occluded, a stretch of the walls of the thoracic aorta, performed without obstructing aortic flow, induced a significant reflex increase in arterial pressure (35 ± 2−26 ± 1 mmHg; systolic–diastolic). This pressure increase was accompanied by significant increases in peripheral resistance in the superior mesenteric (+30%), renal (+23%), and external iliac (+23%) vascular beds. The increase in iliac resistance observed in the skinned leg was comparable with that observed in the contralateral intact limb. All these vascular responses were drastically reduced by the administration of phenoxybenzamine. After α-adrenergic blockade no signs of reflex vasodilatation could be detected during aortic stretch in any of the vascular beds examined.

Circulatory responses to a CO2 buffer following lethal injections of endotoxin

1961 ◽  
Vol 200 (4) ◽  
pp. 751-754 ◽  
Author(s):  
Lerner B. Hinshaw ◽  
James A. Vick ◽  
David L. Nelson ◽  
Lorentz E. Wittmers ◽  
Orville P. Swenson
Keyword(s):  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Venous Return ◽  
Intact Animal ◽  
Peripheral Resistance ◽  
Tissue Fluid ◽  
Vascular Effect ◽  
Arterial Inflow ◽  
Prolonged Hypotension ◽  
Total Body

The circulatory actions of a CO2 buffer (THAM) have been studied in the isolated perfused dog leg and kidney and in the intact dog. Techniques involving controlled arterial inflow were used in order that changes in vascular resistance could be calculated. Changes in organ weight were correlated with alterations in vascular resistance and hematocrit. Cardiac inflow was controlled and monitored in total body perfusion experiments in order that total peripheral resistance calculations and changes in venous return could be readily obtained. The infusion of THAM results in marked decreases in vascular resistance of leg, kidney and the totally perfused intact animal. Following the onset of THAM infusion there is a significant increase in venous return, brought about primarily by the reabsorption of tissue fluid. The vascular effect of THAM on the kidney may account for the profound diuretic action, although its use during prolonged hypotension appears to be detrimental. The findings of the present study indicate that the possible uses of THAM in hypertension and edema are worthy of investigation.

Contribution of Stenosis Resistance to the Rise in total Peripheral Resistance during Experimental Renal Hypertension in Conscious Dogs

1981 ◽  
Vol 61 (6) ◽  
pp. 663-670 ◽  
Author(s):  
W. P. Anderson ◽  
P. I. Korner ◽  
J. A. Angus ◽  
C. I. Johnston
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Plasma Renin Activity ◽  
Renal Artery ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Plasma Renin ◽  
Vascular Beds ◽  
Renal Vascular

1. Mild, moderate and severe renal artery stenosis was induced in uninephrectomized conscious dogs by inflating a renal artery cuff to lower distal pressure to 60, 40 or 20 mmHg respectively. The renal artery was narrowed progressively over the next 3 days by further inflation of the cuff to relower the distal renal artery pressure to the initial values. 2. Graded progressive stenosis produced graded progressive rises in blood pressure, plasma renin activity and total renal resistance to flow over the 3 day period, followed by a return to control values 24 h after cuff deflation. 3. The rise in total renal resistance to flow was almost entirely due to the stenosis, with only small changes occurring in renal vascular resistance. 4. in moderate and severe stenosis cardiac output did not alter significantly and thus increases in blood pressure were due to increases in total peripheral resistance. in these groups the resistance to blood flow of the stenosis accounted respectively for about 36 and 26% of the rises in total peripheral resistance. Vasoconstriction of the other non-renal vascular beds accounted for the remainder of the increase in total peripheral resistance. 5. in mild stenosis the changes in both cardiac output and total peripheral resistance were variable and not statistically significant. in this group the rise in stenosis resistance was compensated by vasodilatation of the non-renal vascular beds. 6. in all groups rises in plasma renin activity and blood pressure correlated with the haemodynamic severity of the stenosis. 7. Thus the resistance to blood flow of the moderate and severe renal artery stenoses accounted for one-quarter to one-third of the increases in total peripheral resistance. The remainder of the increase in total peripheral resistance was due to vasoconstriction of nonrenal beds.

Microvascular rarefaction and tissue vascular resistance in hypertension

1989 ◽  
Vol 256 (1) ◽  
pp. H126-H131 ◽  
Author(s):  
A. S. Greene ◽  
P. J. Tonellato ◽  
J. Lui ◽  
J. H. Lombard ◽  
A. W. Cowley
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Flow Distribution ◽  
Cheek Pouch ◽  
Tissue Blood Flow ◽  
Hamster Cheek Pouch ◽  
Relative Contribution ◽  
Microvascular Rarefaction

The purpose of this study was to quantitatively estimate the relative contribution of arteriolar rarefaction (disappearance of microvessels) and arteriolar constriction to the increases in total peripheral resistance and changes in the patterns of flow distribution observed in hypertension. A mathematical model of the hamster cheek pouch intraluminal microcirculation was constructed based on data from the literature and observations from our own laboratory. Separate rarefaction and constriction of third-order (3A) and fourth-order (4A) arterioles were performed on the model, and the results were quantified based on the changes of the computed vascular resistance. The degree of increase in resistance depended both on the number and the order of vessels rarefied or constricted and also on the position of those vessels in the network. The maximum increases in resistance obtained in the model runs were 21% for rarefaction and 75% for constriction. Rarefaction, but not constriction, produced large increases in the degree of heterogeneity of blood flow in the various vessel orders. These results demonstrate that vessel rarefaction significantly influences tissue blood flow resistance to a degree comparable with vessel constriction; however, unlike constriction, microvascular rarefaction markedly altered blood flow distribution in our model of the hamster cheek pouch vascular bed. These findings conform with the hypothesis that a significant component of the increase in total peripheral resistance in hypertension may be due to vessel rarefaction.

scholarly journals Mechanisms mediating NTS P2x receptor-evoked hypotension: cardiac output vs. total peripheral resistance

2001 ◽  
Vol 281 (5) ◽  
pp. H2198-H2203 ◽  
Author(s):  
Amy M. Kitchen ◽  
Heidi L. Collins ◽  
Stephen E. DiCarlo ◽  
Tadeusz J. Scislo ◽  
Donal S. O'Leary
Keyword(s):  
Cardiac Output ◽  
Total Peripheral Resistance ◽  
Nucleus Tractus Solitarius ◽  
Peripheral Resistance ◽  
P2x Receptor ◽  
High Dose ◽  
Sprague Dawley ◽  
Relative Contribution ◽  
Sprague Dawley Rats ◽  
Filling Time

We have previously shown that P2x purinoceptor activation in the subpostremal nucleus tractus solitarius (NTS) produces dose-dependent decreases in mean arterial pressure (MAP), heart rate, efferent sympathetic nerve activity, and significant peripheral vasodilation. However, the relative roles of cardiac output (CO) and total peripheral resistance (TPR) in mediating this depressor response are unknown. Bradycardia does not necessarily result in decreased CO, because, with the greater filling time, stroke volume may increase such that CO may be unchanged. We measured changes in CO (via a chronically implanted flow probe on the ascending aorta) and MAP in α-chloralose- and urethane-anesthetized male Sprague-Dawley rats in response to microinjection of the selective P2x purinoceptor agonist α,β-methylene ATP (25 and 100 pmol/50 nl) into the subpostremal NTS. TPR was calculated as MAP/CO. At the low dose of NTS P2x purinoceptor agonist, the reduction in MAP was primarily mediated by reductions in TPR (−31.3 ± 3.3%), not CO (−8.7 ± 1.7%). At the high dose, both CO (−34.4 ± 6.6%) and TPR (−40.2 ± 2.5%) contribute to the reduction in MAP. We conclude that the relative contribution of CO and TPR to the reduction in MAP evoked by NTS P2x purinoceptor activation is dependent on the extent of P2x purinoceptor activation.

Cardiovascular Effects of Moxibustion at Jen Chung (Go-26) during Halothane Anesthesia in Dogs

1975 ◽  
Vol 03 (03) ◽  
pp. 245-261 ◽  
Author(s):  
Do Chil Lee ◽  
Myung O. Lee ◽  
Donald H. Clifford
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Stroke Volume ◽  
Total Peripheral Resistance ◽  
Venous Pressure ◽  
Peripheral Resistance ◽  
Cardiovascular Effects ◽  
Halothane Anesthesia

The cardiovascular effects of moxibustion at Jen Chung (Go-26) in 10 dogs under halothane anesthesia were compared to 5 dogs under halothane anesthesia without moxibustion and 5 dogs under halothane anesthesia in which moxibustion was effected at a neutral or non-acupuncture site. Cardiac output, stroke volume, heart rate, mean arterial pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2 and base deficit were measured over a two-hour period. A significant increase in cardiac output and stroke volume and a significant decrease in the total peripheral resistance were observed in the group which was stimulated by moxibustion at Jen Chun (Go-26). Heart rate, mean arterial pressure and pulse pressure were significantly increase during the early part of the two-hour period in the same group. The cardiovascular effects of moxibustion at Jen Chung (Go-26) which were observed at the end of the two hours were also present in two dogs in which measurements were continued for two additional hours.

Effect of orthotopic transplantation of liver on systemic and splanchnic hemodynamics in conscious rat

1995 ◽  
Vol 269 (1) ◽  
pp. G153-G159 ◽  
Author(s):  
L. V. Kuznetsova ◽  
D. Zhao ◽  
A. M. Wheatley
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Portal Pressure ◽  
Peripheral Resistance ◽  
Vena Cava ◽  
Cardiovascular Effects ◽  
Suture Technique ◽  
Arterial Blood Flow ◽  
Conscious Rat ◽  
Arterial Blood

The long-term cardiovascular effects of orthotopic liver transplantation (OLT) were studied in conscious Lewis rats with a radioactive microsphere technique. Three months after OLT with an all-suture technique for graft revascularization (s-OLT), all hemodynamic parameters were similar to control. OLT with "cuffs" fitted to the portal vein and infrahepatic inferior vena cava (c-OLT) led to prominent hemodynamic disturbances including 1) hyperkinetic circulation with increased cardiac index (CI; 22%; P < 0.05) and decreased mean arterial pressure (15%; P < 0.05) and total peripheral resistance (TPR; 28%; P < 0.05); 2) a slight increase in portal pressure (11.8 +/- 0.9 vs. 9.3 +/- 1.7 mmHg in control) and marked portal-systemic shunting (51 +/- 11 vs. 0.05 +/- 0.04% in control; P < 0.05); 3) increased hepatic arterial blood flow (0.49 +/- 0.06 vs. 0.27 +/- 0.04 ml.min-1.g liver wt-1; P < 0.05); 4) splanchnic vasodilation with vascular resistance significantly (P < 0.05) lower in the liver, stomach, and large intestine; and 5) increased blood flow and decreased vascular resistance in the kidneys and heart. Ganglionic blockade with chlorisondamine (5 mg/kg body wt iv) indicated that the increase in CI seen in the c-OLT rats was probably sympathetically mediated, whereas the increase in renal blood flow was a reflection of the increase in CI. After ganglionic blocker administration, TPR and regional vascular resistances decreased to approximately the same extent in the control and c-OLT groups, indicating that vascular sympathetic tone was unchanged in the c-OLT rats.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Hemodynamic variables in piglets anesthetized with isoflurane or propofol, kept under spontaneous ventilation and FIO2 of 0.5

2019 ◽  
Vol 71 (6) ◽  
pp. 1846-1852
Author(s):  
C.K. Ido ◽  
P.E.S. Silva ◽  
H.R.A. Silva ◽  
E.G.F. Biteli ◽  
R.L. Carneiro ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Venous Pressure ◽  
Peripheral Resistance ◽  
Resistance Index ◽  
Spontaneous Ventilation ◽  
Stroke Index ◽  
Hemodynamic Variables

ABSTRACT This study aimed to evaluate comparatively the effects of propofol or isoflurane on hemodynamic variables in piglets that received inspired oxygen fraction (FIO2) of 0.5 under spontaneous ventilation. Therefore, sixteen piglets weighing 16±1.1kg, were randomly divided into two groups: GI (Isoflurane and FIO2 of 0.5) and GP (Propofol and FIO2 of 0.5). Heart rate (HR), systolic, diastolic and mean arterial pressure (SAP, DAP and MAP), central venous pressure (CVP), cardiac output (CO), mean pulmonary arterial pressure (mPAP) and mean capillary pulmonary pressure (mCPP) were assessed 40 minutes after anesthetic induction (T0), followed by 15 minutes intervals (from T15 to T60). The variables cardiac index (CI), stroke volume (SV), stroke index (SI), total peripheral resistance (TPR), total peripheral resistance index (TPRI), pulmonary vascular resistance (PVR), and pulmonary vascular resistance index (PVRI) were calculated. SAP and TPRI were significantly different between groups at T30 and T60 (P< 0.05) with higher GP values being recorded. There were no differences in the other variables, however, GP presented mean closer to normality on most of the analyzed variables. Therefore, we conclude that total intravenous anesthesia with propofol presented greater stability of the hemodynamic variables evaluated.

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