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 (<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.

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.

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.

scholarly journals Sex differences in sympathetic vasoconstrictor responsiveness and sympatholysis

2017 ◽  
Vol 123 (1) ◽  
pp. 128-135 ◽  
Author(s):  
Timothy P. Just ◽  
Darren S. DeLorey
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Sex Differences ◽  
Muscle Contraction ◽  
Vascular Resistance ◽  
Triceps Surae ◽  
Female Rats ◽  
Male Rats ◽  
Sympathetic Chain ◽  
Sympathetic Vasoconstriction

Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of sex have not been fully elucidated. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle, and estrogen modulates NO synthase (NOS) expression and NO bioavailability. Therefore NO-mediated inhibition of sympathetic vasoconstriction may be enhanced in females. Thus the purpose of the present study was to investigate the hypothesis that sympathetic vasoconstrictor responsiveness would be blunted and NO-mediated inhibition of sympathetic vasoconstriction would be enhanced in females compared with males. Male (M; n = 8) and female (F; n = 10) Sprague-Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS blockade [ Nω-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented ( P < 0.05) in female compared with male rats at 2 Hz [F: −33 ± 8% (SD); M: −26 ± 6%] but was not different at 5 Hz (F: −55 ± 7%; M: −47 ± 7%). During muscle contraction, evoked vasoconstriction was similar ( P > 0.05) in females and males at 2 Hz (F: −12 ± 5%; M: −13 ± 5%) but was blunted ( P < 0.05) in females compared with males at 5 Hz (F: −24 ± 5%; M: −34 ± 8%). l-NAME increased ( P < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced ( P < 0.05) in females compared with males; however, sympatholysis was not different ( P > 0.05) between males and females in the presence of NOS blockade, indicating that NO-mediated sympatholysis was augmented in female rats. These data suggest that sex modulates sympathetic vascular control in resting and contracting skeletal muscle and that a portion of the enhanced sympatholysis in female rats was NO dependent. NEW & NOTEWORTHY Sex differences in the neurovascular regulation of blood pressure and vascular resistance have been documented. However, our understanding of the underlying mechanisms that mediate these differences is incomplete. The present study demonstrates that female rats have an enhanced capacity to inhibit sympathetic vasoconstriction during exercise (sympatholysis) and that NO mediates a portion of the enhanced sympatholysis.

Effect of insulin on regional vascular resistances in conscious rats

1996 ◽  
Vol 270 (2) ◽  
pp. R450-R455
Author(s):  
E. Qadir ◽  
J. P. Porter
Keyword(s):  
Skeletal Muscle ◽  
Arterial Pressure ◽  
Low Dose ◽  
Chronic Administration ◽  
High Dose ◽  
Ganglionic Blockade ◽  
Conscious Rats ◽  
Before And After ◽  
Vascular Beds ◽  
Renal Vascular

In the rat, but not in humans and other mammals, chronic administration of insulin produces hypertension. The present aim was to determine the effect of acute insulin infusion on regional vascular resistances and to determine the neurogenic contribution to the response. Conscious rats were infused with insulin (2 or 6 mU/min) before and after ganglionic blockade with chlorisondamine (5 mg/kg). The low dose of insulin produced an increase in arterial pressure and hindquarter vascular resistance; the high dose produced a gradual decrease in arterial pressure and renal resistance. After ganglionic blockade, the hindquarter vasoconstriction produced by the low dose was abolished. The high dose of insulin produced both hindquarter and renal vasodilation. Thus the low dose of insulin had a selective neurogenic vasoconstrictor effect in rat skeletal muscle vascular beds. With higher doses, direct vasodilatory effects in both skeletal muscle and renal vascular beds appeared. This greater sensitivity of the sympathoexcitatory effects of insulin in rats may explain the ability of chronic insulin infusions to increase blood pressure in this species.

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)

TNFα Mechanically Sensitizes Masseter Muscle Afferent Fibers of Male Rats

2009 ◽  
Vol 102 (3) ◽  
pp. 1551-1559 ◽  
Author(s):  
Akhlaq W. Hakim ◽  
Xu-Dong Dong ◽  
Peter Svensson ◽  
Ujendra Kumar ◽  
Brian E. Cairns
Keyword(s):  
Skeletal Muscle ◽  
Masseter Muscle ◽  
Receptor Activation ◽  
Male Rats ◽  
Blue Dye ◽  
Necrosis Factor Alpha ◽  
Protein Extravasation ◽  
Behavioral Evidence ◽  
Ganglion Neurons ◽  
P75 Receptor

Behavioral evidence in rats indicates that injection of tumor necrosis factor alpha (TNFα) into skeletal muscle results in a prolonged mechanical sensitization without gross inflammation. To investigate whether a peripheral mechanism could underlie this effect, in the present study, TNFα (1 or 0.1 μg) was injected into the rat masseter muscle to assess its effect on the excitability and mechanical threshold (MT) of muscle nociceptors as well as on inflammation. Expression of TNFR1 (P55 receptors) and TNFR2 (P75 receptors) by the masseter muscle and trigeminal ganglion neurons that innervate that muscle was determined by Western blot and immunohistochemistry, respectively. The Evans blue dye technique was used at the end of the TNFα experiments to assess for plasma protein extravasation. In subsequent experiments to confirm the involvement of receptor activation in TNFα-induced effects, P55 or P75 receptor antibody was co-injected with TNFα. Intramuscular injection of 1 μg TNFα did not excite nociceptors but did significantly decrease MT compared with vehicle control. There was no evidence of gross inflammation 3 h after injection of TNFα. Co-injection of TNFα with P55 or P75 receptor antibodies attenuated TNFα-induced mechanical sensitization. P55 and P75 receptors were expressed by 29 and 62% of masseter nociceptors, respectively. These findings indicate that TNFα induces mechanical sensitization of masseter nociceptors that is mediated through activation of peripheral P55 and P75 receptors. These results support the hypothesis that a peripheral receptor mechanism could contribute to TNFα-induced noninflammatory mechanical sensitization of skeletal muscle previously reported in behaving rats.

Cardiovascular actions of ANF: contributions of renal, neurohumoral, and hemodynamic factors in sheep

1993 ◽  
Vol 264 (3) ◽  
pp. R533-R538 ◽  
Author(s):  
C. J. Charles ◽  
E. A. Espiner ◽  
A. M. Richards
Keyword(s):  
Arterial Pressure ◽  
Low Dose ◽  
Pressor Response ◽  
Peripheral Resistance ◽  
Systolic Arterial Pressure ◽  
Cardiovascular Effects ◽  
Ang Ii ◽  
Hypotensive Action ◽  
The Difference ◽  
Conscious Sheep

Whereas the short-term effects of atrial natriuretic factor (ANF) are well documented, less is known concerning the possible hypotensive action of sustained low-dose ANF infusions. Accordingly, we have examined the sequential renal, hormonal, and hemodynamic responses to 48-h low-dose ANF infusions in eight normotensive conscious sheep and evaluated the effects of these infusions on autonomic (baroreceptor), adrenocortical, and pressor responsiveness to exogenous stimulation. Plasma ANF levels tended to rise in response to ANF infusions, but the difference between ANF and control day levels was not significantly different. Systolic arterial pressure (SAP) was significantly lower after ANF infusion (P = 0.01) and was associated with a reduction in calculated total peripheral resistance (CTPR, P = 0.007). Mean arterial pressure also tended to be lower (P = 0.08) in response to ANF. No change was seen in urinary volume or sodium excretion or in plasma angiotensin II (ANG II), aldosterone, or cortisol levels. ANF significantly attenuated the pressor response to exogenous ANG II (P = 0.01) but did not affect the adrenocortical responsiveness or autonomic (baroreceptor) responsiveness to exogenous stimulation. This study demonstrates that chronic low-dose infusions of ANF that barely elevate plasma ANF levels induce significant cardiovascular effects, including lowering of SAP associated with a fall in CTPR and attenuation of pressor responsiveness to physiological increments in ANG II, thus providing further support for the importance of ANF in blood pressure homeostasis in normal sheep.

scholarly journals Hypertrophy of Rat Skeletal Muscle Is Associated with Increased SIRT1/Akt/mTOR/S6 and Suppressed Sestrin2/SIRT3/FOXO1 Levels

2021 ◽  
Vol 22 (14) ◽  
pp. 7588
Author(s):  
Zoltan Gombos ◽  
Erika Koltai ◽  
Ferenc Torma ◽  
Peter Bakonyi ◽  
Attila Kolonics ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Hypertrophy ◽  
Male Rats ◽  
Cellular Interactions ◽  
Molecular Signaling ◽  
Protein Breakdown ◽  
Rat Skeletal Muscle ◽  
Plantaris Muscle ◽  
Skeletal Muscle Hypertrophy ◽  
Intensive Investigation

Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-β-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.

Caloric restriction following early-life high fat-diet feeding represses skeletal muscle TNF in male rats

2021 ◽  
Vol 91 ◽  
pp. 108598
Author(s):  
Diego Hernández-Saavedra ◽  
Laura Moody ◽  
Xinyu Tang ◽  
Zachary J. Goldberg ◽  
Alex P. Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Caloric Restriction ◽  
High Fat Diet ◽  
Early Life ◽  
Male Rats ◽  
High Fat

scholarly journals Vulnerability factors for mephedrone-induced conditioned place preference in rats—the impact of sex differences, social-conditioning and stress

2021 ◽  
Author(s):  
Olga Wronikowska ◽  
Maria Zykubek ◽  
Łukasz Kurach ◽  
Agnieszka Michalak ◽  
Anna Boguszewska-Czubara ◽  
...  
Keyword(s):  
Sex Differences ◽  
Conditioned Place Preference ◽  
Low Dose ◽  
Social Factor ◽  
Place Preference ◽  
Female Rats ◽  
Male Rats ◽  
Social Conditioning ◽  
Male And Female Rats ◽  
The Impact

Abstract Rationale Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood. Objectives The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats. Methods The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively. Results Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus. Conclusions Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

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