Sympathetic Arterial Pressure Regulation Research Articles

Acute effects of empagliflozin on open-loop baroreflex function and urine output in streptozotocin-induced type 1 diabetic rats

Although sympathetic suppression is considered one of the mechanisms for cardioprotection afforded by sodium–glucose cotransporter 2 (SGLT2) inhibitors, whether SGLT2 inhibition acutely modifies sympathetic arterial pressure (AP) regulation remains unclear. We examined the acute effect of an SGLT2 inhibitor, empagliflozin (10 mg/kg), on open-loop baroreflex static characteristics in streptozotocin (STZ)-induced type 1 diabetic and control (CNT) rats (n = 9 each). Empagliflozin significantly increased urine flow [CNT: 25.5 (21.7–31.2) vs. 55.9 (51.0–64.5), STZ: 83.4 (53.7–91.7) vs. 121.2 (57.0–136.0) μL·min−1·kg−1, median (1st–3rd quartiles), P < 0.001 for empagliflozin and STZ]. Empagliflozin decreased the minimum sympathetic nerve activity (SNA) [CNT: 15.7 (6.8–18.4) vs. 10.5 (2.9–19.0), STZ: 36.9 (25.7–54.9) vs. 32.8 (15.1–37.5) %, P = 0.021 for empagliflozin and P = 0.003 for STZ], but did not significantly affect the peripheral arc characteristics assessed by the SNA–AP relationship. Despite the significant increase in urine flow and changes in several baroreflex parameters, empagliflozin preserved the overall sympathetic AP regulation in STZ-induced diabetic rats. The lack of a significant change in the peripheral arc may minimize reflex sympathetic activation, thereby enhancing a cardioprotective benefit of empagliflozin.

Acute effects of empagliflozin on open-loop baroreflex function and urine glucose excretion in Goto-Kakizaki diabetic rats

Although suppression of sympathetic activity is suggested as one of the underlying mechanisms for the cardioprotective effects afforded by sodium–glucose cotransporter 2 (SGLT2) inhibitors, whether the modulation of glucose handling acutely affects sympathetic regulation of arterial pressure remains to be elucidated. In Goto–Kakizaki diabetic rats, we estimated the open-loop static characteristics of the carotid sinus baroreflex together with urine glucose excretion using repeated 11-min step input sequences. After the completion of the 2nd sequence, an SGLT2 inhibitor empagliflozin (10 mg kg−1) or vehicle solution was administered intravenously (n = 7 rats each). Empagliflozin did not significantly affect the baroreflex neural or peripheral arc, despite significantly increasing urine glucose excretion (from 0.365 ± 0.216 to 8.514 ± 0.864 mg·min−1·kg−1, P < 0.001) in the 7th and 8th sequences. The possible sympathoinhibitory effect of empagliflozin may be an indirect effect associated with chronic improvements in renal energy status and general disease conditions.

Does COVID‐19 influence the sympathetic regulation of blood pressure?

Does COVID‐19 influence the sympathetic regulation of blood pressure?

Intense Fear Induces Low‐Frequency Oscillation of Cerebral Blood Flow, Arterial Pressure, and Sympathetic Nerve Activity in Conscious Rats

A traumatic event, such as disaster, causes intense fear, which potentially leads to an increase in occurrence of cerebrovascular diseases. Little information is available regarding why intense fear causes cerebrovascular diseases. The present study aimed to measure cerebral blood flow, arterial pressure, and sympathetic nerve activity during intense fear conditioning in conscious rats. Wistar rats were chronically instrumented with a probe made with glass fiber for measuring hippocampal cerebral blood flow. Electrodes for measurements of renal (RSNA) and lumbar sympathetic nerve activity (LSNA) were inserted, as well as for an electroencephalogram, electromyogram, and electrocardiogram. A catheter was inserted for measuring systemic arterial pressure. Standard fear‐conditioning trials, in which a tone was paired with a brief electrical shock (5 mA, 2 s), were performed in rats two times per day over 3 days. Oscillation of arterial pressure with an amplitude of 15.7 mmHg and frequency of 0.075 Hz was induced by exposing a tone without electrical shock in fear‐conditioned rats. Arterial pressure oscillation was associated with synchronized oscillation of hippocampal cerebral blood flow, RSNA, and LSNA. Coherence between arterial pressure and hippocampal cerebral blood flow, RSNA, and LSNA was significantly increased at low frequency (0–1 Hz) compared with naive rats. These data suggest that intense fear can trigger disorder of sympathetic regulation of arterial pressure, causing low‐frequency oscillation of arterial pressure and synchronized changes in cerebral blood flow. This may be one of the causes of cerebrovascular disease induced by intense fear.Support or Funding InformationJSPS GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sex, drugs and blood pressure control: the impact of age and gender on sympathetic regulation of arterial pressure

Cardiovascular disease is the leading cause of death in developed countries. Numerous studies confirm that increases in blood pressure occur with ageing, and are associated with an increased risk of cardiovascular events. The effects of ageing on the cardiovascular system and blood pressure control differ between males and females, but the mechanisms underlying this remain unclear (Hart et al. 2009a). Starting in puberty, men tend to have higher blood pressures compared with women; this difference continues until women reach menopause, at which point the incidence of hypertension begins to increase rapidly, often exceeding that of men (Hart et al. 2009a). This has led to the suggestion that female sex hormones exhibit a cardio-protective effect in younger women, although this has not been proven. This article focuses on a recent paper published in The Journal of Physiology by Hart et al. (2011) that illustrates the specific cardiovascular parameters that underlie sex- and age-related differences in sympathetic activity and resting blood pressure. The paper also provides novel mechanistic insight into the role of the sympathetic nervous system in the development of hypertension with age, with a particular emphasis on the effect of menopause on the risk of hypertension in women. We will first examine the findings of this article in context with previous studies in this field, and then provide a thoughtful discussion on the complexity of this article's findings.

Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Obesity-Induced Hypertension

Obesity is one of the major risk factors for cardiovascular disease and is often associated with increased oxidative stress and sympathoexcitation. We have already suggested that increased oxidative stress in the brain modulates the sympathetic regulation of arterial pressure in salt-sensitive hypertension, which is often associated with obesity. The present study was performed to determine whether oxidative stress could mediate central sympathoexcitation in the initial stage of obesity-induced hypertension. Four-week-old male Sprague-Dawley rats were fed a high-fat (45% kcal as fat) or low-fat (10% kcal as fat) diet for 6 weeks. Fat loading elicited hypertension and sympathoexcitation, along with visceral obesity. In urethane-anesthetized and artificially ventilated rats, arterial pressure and renal sympathetic nerve activity decreased in a dose-dependent fashion when 53 or 105 mumol/kg tempol, a membrane-permeable superoxide dismutase mimetic, was infused into the lateral cerebral ventricle. Central tempol reduced arterial pressure and renal sympathetic nerve activity to a significantly greater extent in high-fat diet-fed hypertensive rats than in low-fat diet-fed normotensive rats. Intracerebroventricular apocynin or diphenyleneiodonium, a reduced NADPH oxidase inhibitor, also elicited markedly greater reductions in arterial pressure and renal sympathetic nerve activity in the high-fat diet-fed rats. In addition, fat loading increased NADPH oxidase activity and NADPH oxidase subunit p22(phox), p47(phox), and gp91(phox) mRNA expression in the hypothalamus. In obesity-induced hypertension, increased oxidative stress in the brain, possibly via activation of NADPH oxidase, may contribute to the progression of hypertension through central sympathoexcitation.

Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Salt-Sensitive Hypertension

Central sympathoexcitation is involved in the pathogenesis of salt-sensitive hypertension. We have suggested that oxidative stress in the brain modulates the sympathetic regulation of arterial pressure. Thus, we investigated whether oxidative stress could mediate central sympathoexcitation in salt-sensitive hypertension. Five- to 6-week-old male Dahl salt-sensitive rats and salt-resistant rats were fed with a normal (0.3%) or high- (8%) salt diet for 4 weeks. In urethane-anesthetized and artificially ventilated rats, arterial pressure, renal sympathetic nerve activity, and heart rate decreased in a dose-dependent fashion, when 20 or 40 micromol of tempol, a membrane-permeable superoxide dismutase mimetic, was infused into the lateral cerebral ventricle. The same degree of reduction was noted in salt-sensitive and salt-resistant rats without salt loading. Salt loading significantly increased central tempol-induced reductions in arterial pressure (-29.1+/-4.8% versus -10.6+/-3.3% at 40 micromol; P<0.01), sympathetic nerve activity (-18.7+/-2.0% versus -7.1+/-1.8%; P<0.01), and heart rate (-10.7+/-2.8% versus -2.0+/-0.7%; P<0.05) in salt-sensitive rats but not in salt-resistant rats. Intracerebroventricular diphenyleneiodonium, a reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, also elicited significantly greater reduction in each parameter in salt-loaded salt-sensitive rats. Moreover, salt loading increased reduced nicotinamide-adenine dinucleotide phosphate-dependent superoxide production in the hypothalamus in salt-sensitive rats but not in salt-resistant rats. In addition, reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits p22(phox), p47(phox), and gp91(phox) mRNA expression significantly increased in the hypothalamus of salt-loaded salt-sensitive rats. In conclusion, in salt-sensitive hypertension, increased oxidative stress in the brain, possibly via activation of reduced nicotinamide-adenine dinucleotide phosphate oxidase, may elevate arterial pressure through central sympathoexcitation.