Gain Of Arterial Baroreflex Control Research Articles

Water drinking enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in healthy young humans.

What is the central question of this study? Water drinking increases muscle sympathetic nerve activity (MSNA), and it increases arterial blood pressure (ABP) in older populations but not in young healthy subjects. Does an increase in gain of arterial baroreflex control of MSNA contribute to maintenance of ABP after water drinking in healthy young subjects? What is the main finding and its importance? The gain of arterial baroreflex control of MSNA was increased and remained elevated 60min after water drinking (500ml) but remained unchanged after saline intake. An enhancement in gain of arterial baroreflex control of MSNA contributes to the maintenance of ABP after water drinking in young healthy subjects, probably via osmosensitive mechanisms. Water drinking increases muscle sympathetic nerve activity (MSNA), which is accompanied by a profound pressor response in patients with impaired arterial baroreflex function and in older populations, but not in healthy young subjects. We tested the hypothesis that an enhancement in the gain of arterial baroreflex control of MSNA contributes to the maintenance of arterial blood pressure after water drinking in healthy young subjects. The MSNA, arterial blood pressure and heart rate were measured in 10 healthy men (24± 2 years old; mean ± SD) before and for 60min after ingestion of 500ml of bottled water or saline solution. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. After water drinking, MSNA was significantly elevated within 15min and remained above baseline for up to 60min [e.g. 21± 10bursts (100heart beats)-1 mmHg-1 at baseline versus 35± 14 bursts (100heart beats)-1 mmHg-1 at 30min; P< 0.01], whereas mean arterial blood pressure (e.g. 87± 7mmHg at baseline versus 89± 7mmHg at 30min; P= 0.34) and heart rate were unchanged. The arterial baroreflex-MSNA gain for bursts incidence was increased and remained elevated throughout the protocol [e.g. -2.25± 0.99bursts (100heart beats)-1 mmHg-1 at baseline versus -4.32± 1.53 bursts (100heart beats)-1 mmHg-1 at 30min; P< 0.01]. Importantly, saline intake had no effect on arterial baroreflex-MSNA gain or any neurocardiovascular variables. These findings demonstrate that water drinking enhances the gain of arterial baroreflex control of MSNA in healthy young men, which may contribute to buffering the pressor response after water drinking, probably via osmosensitive mechanisms.

The Effect of Prior Carbohydrate Ingestion on Baroreflex Sensitivity During Light Exercise

Carbohydrate ingestion increases sympathetic activity and hyperinsulinemia enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity at rest. However, the effect of carbohydrate-induced sympathoexcitation on arterial baroreflex sensitivity (BRS) during exercise is not known. PURPOSE: To evaluate the effect of carbohydrate ingestion on BRS during light exercise. METHODS: Ten healthy male subjects (23 ± 1 yr) performed in different days 20 min of cycling at 35% HRR, with and without ingestion of 200 g of glucose (maltodextrin). Capillary blood glucose concentration was measured by fingerstick at rest, 20 min following carbohydrate ingestion and every 5 min during exercise. Systolic blood pressure and pulse interval was measured continuously and non-invasively and BRS was evaluated with the cross-correlation method (xBRS). Comparisons between the two conditions were made using two-way ANOVA with repeated measures. RESULTS: Following carbohydrate ingestion blood glucose increased from baseline (8.2 ± 0.1 vs. 5.1 ± 0.1 to mmol/L, p<0.05, respectively). During exercise heart rate was increased from 70 ± 2 bpm at rest to 115 ± 3 bpm (p<0.05). xBRS decreased following carbohydrate ingestion compared to baseline (8.8 ± 2.6 vs. 11.5 ± 4.5 ms/mmHg, p<0.05, respectively), decreased even further during exercise without carbohydrate ingestion compared to resting baseline (3.6 ± 1.6 vs. 12.1 ± 5.5 ms/mmHg, p<0.05, respectively), while it was even lower during exercise with carbohydrate ingestion (2.5 ± 1.0 ms/mmHg, p<0.05), reaching a nadir (1.6 ± 0.7,ms/mmHg, p<0.05) at the end of exercise with carbohydrate ingestion. CONCLUSION: Carbohydrate ingestion prior to light exercise reduces BRS and adds to the sympathoexcitation of exercise that also reduces BRS. Presumably, the reduction of BRS, which is primarily an index of cardiac vagal tone, reflects the reduced vagal activity and net sympathetic dominance.

The neural interaction between the arterial baroreflex and muscle metaboreflex is preserved in older men

Sympathetic baroreflex sensitivity is increased during selective activation of the skeletal muscle metaboreflex with postexercise ischaemia (PEI) in young adults. However, to date, there are no data demonstrating this neural interaction between the arterial baroreflex and the muscle metaboreflex in healthy older adults. Therefore, the goal of the present study was to examine the influence of healthy ageing on the metabolic component of the exercise pressor reflex and its interaction with the arterial baroreflex in the control of sympathetic outflow. Postexercise ischaemia following static hand grip performed at 30% maximal voluntary contraction was used to isolate muscle metaboreflex activation in young [n = 10; 24 ± 1 years old; resting blood pressure (BP) 116 ± 3/64 ± 3 mmHg] and older men (n = 9; 59 ± 2 years old; resting BP 120 ± 2/77 ± 2 mmHg). Arterial BP (Finometer) and muscle sympathetic nerve activity (MSNA) were measured continuously. Weighted linear regression analysis between MSNA and diastolic BP was used to estimate arterial baroreflex MSNA gain. There were no age-related differences in the increase in mean BP (young, Δ14 ± 3 mmHg versus older, Δ15 ± 2 mmHg; P > 0.05) or MSNA burst frequency (young, Δ11 ± 2 bursts min(-1) versus older, Δ9 ± 1 bursts min(-1); P > 0.05) during PEI. Likewise, the gain of arterial baroreflex control of total MSNA increased to a similar extent in both groups during PEI (young, -4.2 ± 0.9 baseline versus -6.3 ± 1.1 PEI a.u. beat(-1) mmHg(-1); and older, -3.7 ± 1.1 baseline versus -6.7 ± 1.4 PEI a.u. beat(-1) mmHg(-1); P < 0.05 for both). Collectively, these findings indicate that the neural interaction between the arterial baroreflex and the skeletal muscle metaboreflex in the regulation of MSNA is preserved in healthy ageing.

Water drinking enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in healthy humans

Water drinking increases efferent sympathetic outflow in young healthy subjects in the absence of a pressor response, whereas in autonomic failure patients and healthy older adults water‐induced sympatho‐excitation is accompanied by a large pressor response. The extent to which the arterial baroreflex (ABR) buffers the blood pressure (BP) response to water intake is unclear. We tested the hypothesis that water drinking increases ABR control of muscle sympathetic nerve activity (MSNA) in young healthy subjects. MSNA (microneurography) and arterial BP (Finometer) were measured in 8 men (24 ± 1 yrs) before, and for 60 min after drinking 500 mL of room‐temperature (22°C) tap water or saline. Weighted linear regression analysis between MSNA and diastolic BP was used to assess spontaneous ABR MSNA gain. As expected, MSNA was elevated after water intake (22 ± 4 baseline to 36 ± 5 bursts/100 heart beats at 30 min, P&lt;0.05) and BP was unchanged. ABR MSNA gain for burst incidence (−2.4 ± 0.3 baseline vs. −4.4 ± 0.6 bursts/100 heart beats/mmHg at 30 min; P&lt;0.05) and total MSNA (−3.6 ± 0.8 baseline vs. −5.6 ± 0.8 au/beat/mmHg at 30 min; P&lt;0.05) were increased and tended to return to baseline at 60 min. ABR‐MSNA gain remained unchanged following saline intake. These data indicate that ABR MSNA gain is enhanced following water intake in healthy young subjects, which likely contributes to the maintenance of BP.Supported by CAPES, CNPq &amp; FAPERJ

Insulin: a sweet deal for human baroreflex function

The pancreatic hormone insulin is a metabolic ‘hormone of abundance’. Following postprandial absorption of nutrients, insulin stimulates glucose and amino acid uptake into skeletal muscle and enhances hepatic and adipose tissue glycogen and fatty acid synthesis. However, its actions are considerably more far-reaching. Pancreatic insulin accumulates in the brain via active transport from plasma across the impermeable blood–brain barrier (Banks, 2004). Once in the brain, it binds to insulin receptors present in multiple discrete sites throughout the central nervous system (Banks, 2004). Its central actions include effects on energy balance, such as suppression of food intake and hepatic glucose production. Central insulin also modulates the cardiovascular system via actions on the autonomic nervous system. In humans and animals alike, increases in brain insulin due to, for example, ingestion of a meal trigger increases in muscle sympathetic outflow (Straznicky et al. 2010). This sympathoexcitation is considered teleogically beneficial, since it contributes to arterial pressure maintenance at a time when the splanchnic circulation is dilating to accommodate and disperse absorbed nutrients. Animal studies show that insulin also enhances the function of the major short-acting blood pressure regulation system, the baroreceptor reflex, by increasing baroreflex sensitivity or gain. Increased baroreflex gain in turn allows for even tighter arterial pressure control during postprandial hypotensive challenges. Remarkably, however, whether insulin exerts a similar effect on the baroreflex in humans was uncertain until now. In a recent issue of The Journal of Physiology, Young et al. (2010) address this question in healthy young male subjects. Gain of arterial baroreflex control of muscle sympathetic nerve activity (MSNA) was assessed using measurements of spontaneous baroreflex sensitivity, in which sequences of spontaneously occurring ramps in diastolic blood pressure are correlated to evoked changes in MSNA or heart rate. A particular strength of the study was that insulin was elevated within the physiological range using two approaches. Consumption of a mixed meal elicited endogenous insulin release, and exogenous insulin was infused i.v. while clamping plasma glucose levels at basal levels. In both instances, within 30 min of the increment in insulin, MSNA baroreflex gain nearly doubled. Since the hyperinsulinaemic euglycaemic clamp also quantified insulin sensitivity, these studies further revealed that those individuals with the highest insulin sensitivity also exhibited the greatest increase in MSNA baroreflex gain when insulin levels were raised. The strong correlation between insulin sensitivity and baroreflex gain observed by Young et al. in healthy men suggests an important mechanistic link with pathophysiological implications. Interestingly, several insulin-resistant conditions, such as obesity, hypertension, heart failure, type 2 diabetes mellitus, and pregnancy, are also associated with baroreflex impairment. In humans with obesity or type 2 diabetes, strategies that improve insulin sensitivity, such as weight loss, exercise, or gastric bypass surgery before weight loss, also normalize baroreflex function (Madden et al. 2010; Perugini et al. 2010; Straznicky et al. 2010). However, a major question lurks behind these associations: is insulin a master regulator of baroreflex function? Does insulin resistance contribute to baroreflex impairment in all these conditions? Other questions naturally follow. First, is brain insulin the link between insulin sensitivity and baroreflex function? Obesity is known to impair insulin transport into the brain, causing brain insulin levels to fall (Banks, 2004). But whether the fall in brain insulin contributes to the parallel drop in baroreflex gain in insulin-resistant conditions has not been established in animals or humans. Second, how does insulin resistance suppress transport of insulin into the brain? Third, where and how does insulin in the brain enhance baroreflex function? Fourth, insulin and leptin have divergent sex-specific central effects on food intake (Clegg et al. 2003); is insulin's prominent baroreflex gain-enhancing action observed by Young et al. in men also present in women? With the finding of Young et al. that insulin enhances baroreflex gain in humans, the answers to these questions become more critical, especially when considering the deleterious effects of decreases in baroreflex function. A key issue is an inability to maintain arterial pressure during acute hypotensive challenges. Indeed, pregnant women are at risk for orthostatic hypotension, and peripartum haemorrhage is a major cause of maternal mortality. In addition, impaired baroreflex sensitivity and decreased heart rate variability have been identified as risk factors for subsequent deleterious cardiovascular events in patients with type 2 diabetes mellitus or following myocardial infarction (Head, 2002; Okada et al. 2010). If decreased brain insulin is a common mechanism, then standard of care could include strategies for increasing it in insulin-resistant individuals. Thus, brain insulin may be more than an appetite-suppressing hormone; increased brain insulin could also be a sweet deal for maintenance of normal human baroreflex function.

Insulin enhances the gain of arterial baroreflex control of muscle sympathetic nerve activity in humans

Recent animal studies indicate that insulin increases arterial baroreflex control of lumbar sympathetic nerve activity; however, the extent to which these findings can be extrapolated to humans is unknown. To begin to address this, muscle sympathetic nerve activity (MSNA) and arterial blood pressure were measured in 19 healthy subjects (27 ± 1 years) before, and for 120 min following, two common methodologies used to evoke sustained increases in plasma insulin: a mixed meal and a hyperinsulinaemic euglycaemic clamp. Weighted linear regression analysis between MSNA and diastolic blood pressure was used to determine the gain (i.e. sensitivity) of arterial baroreflex control of MSNA. Plasma insulin was significantly elevated within 30 min following meal intake (34 ± 6 uIU ml(1); P < 0.05) and remained above baseline for up to 120 min. Similarly, after meal intake, arterial baroreflex-MSNA gain for burst incidence and total MSNA was increased and remained elevated for the duration of the protocol (e.g. burst incidence gain: 3.29 ± 0.54 baseline vs. 5.64 ± 0.67 bursts (100 heart beats)(1) mmHg(1) at 120 min; P < 0.05). During the hyperinsulinaemic euglycaemic clamp, in which insulin was elevated to postprandial concentrations (42 ± 6 μIU ml(1); P < 0.05), while glucose was maintained constant, arterial baroreflex-MSNA gain was similarly enhanced (e.g. burst incidence gain: 2.44 ± 0.29 baseline vs. 4.74 ± 0.71 bursts (100 heart beats)(1) mmHg(1) at 120 min; P < 0.05). Importantly, during time control experiments, with sustained fasting insulin concentrations, the arterial baroreflex-MSNA gain remained unchanged. These findings demonstrate, for the first time in healthy humans, that increases in plasma insulin enhance the gain of arterial baroreflex control of MSNA.

Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate

Systemic corticosterone (Cort) modulates arterial baroreflex control of both heart rate and renal sympathetic nerve activity. Because baroreceptor afferents terminate in the dorsal hindbrain (DHB), an area with dense corticosteroid receptor expression, we tested the hypothesis that prolonged activation of DHB Cort receptors increases the midpoint and reduces the gain of arterial baroreflex control of heart rate in conscious rats. Small (3-4 mg) pellets of Cort (DHB Cort) or Silastic (DHB Sham) were placed on the surface of the DHB, or Cort was administered systemically by placing a Cort pellet on the surface of the dura (Dura Cort). Baroreflex control of heart rate was determined in conscious male Sprague Dawley rats on each of 4 days after initiation of treatment. Plots of arterial pressure vs. heart rate were analyzed using a four-parameter logistic function. After 3 days of treatment, the arterial pressure midpoint for baroreflex control of heart rate was increased in DHB Cort rats (123 +/- 2 mmHg) relative to both DHB Sham (108 +/- 3 mmHg) and Dura Cort rats (109 +/- 2 mmHg, P < 0.05). On day 4, baseline arterial pressure was greater in DHB Cort (112 +/- 2 mmHg) compared with DHB Sham (105 +/- 2 mmHg) and Dura Cort animals (106 +/- 2 mmHg, P < 0.05), and the arterial pressure midpoint was significantly greater than mean arterial pressure in the DHB Cort group only. Also on day 4, maximum baroreflex gain was reduced in DHB Cort (2.72 +/- 0.12 beats x min(-1) x mmHg(-1)) relative to DHB Sham and Dura Cort rats (3.51 +/- 0.28 and 3.37 +/- 0.27 beats x min(-1) x mmHg(-1), P < 0.05). We conclude that Cort acts in the DHB to increase the midpoint and reduce the gain of the heart rate baroreflex function.

ANG II receptor blockade and arterial baroreflex regulation of renal nerve activity in cardiac failure.

In cardiac failure, efferent renal sympathetic nerve activity (ERSNA) and the activity of the renin-angiotensin system are increased, and arterial baroreflex regulation of ERSNA is attenuated. We examined the effect of intravenous and intracerebroventricular angiotensin II AT receptor blockade with losartan on the arterial baroreflex regulation of ERSNA in conscious control (C) and congestive heart failure (CHF) rats. Intravenous losartan (10 mg/kg, 21.7 mumol/kg) decreased arterial pressure more in CHF than in C rats (-28 +/- 3 vs. -20 +/- 3 mmHg, P < 0.05). After restoration of arterial pressure to the prelosartan value with methoxamine infusion, ERSNA was decreased more in CHF than in C rats (-23 +/- 4 vs. -1 +/- 2%, P < 0.05). Maximal gain of arterial baroreflex control of ERSNA (Gmax) was lower in CHF compared with C rats (-1.94 +/- 0.10 vs. -3.78 +/- 0.21%/mmHg, P < 0.05). Intravenous losartan increased Gmax in CHF (to -3.01 +/- 0.14%/mmHg, P < 0.05) but not in C rats (to -3.56 +/- 0.19%/mmHg). Intracerebroventricular losartan (4.61 micrograms, 10 nmol) did not affect arterial pressure but decreased ERSNA more in CHF than in C rats (-13 +/- 2 vs. -8 +/- 3%, P < 0.05). Like intravenous losartan, intracerebroventricular losartan increased Gmax in CHF (from -2.11 +/- 0.18 to -3.21 +/- 0.30%/mmHg, P < 0.05) but not in C rats (from -3.98 +/- 0.25 to -3.84 +/- 0.22%/mmHg). These results suggest that increased activity of the renin-angiotensin system contributes to the increase in ERSNA and its abnormal arterial baroreflex regulation in cardiac failure.

Effects of high salt intake on control of hindlimb vascular resistance by arterial baroreflex and vagal afferents in spontaneously hypertensive rats.

1. This study aimed to examine whether a high salt diet alters control of vascular resistance by arterial baroreflex and vagal afferents in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). 2. SHR and WKY aged 8 weeks were fed either high (8%) or normal salt (0.4%) diet for 4 weeks. Arterial baroreflex control of hindlimb vascular resistance was assessed by examining reflex-induced vasodilation and vasoconstriction in response to phenylephrine and nitroprusside, respectively, in the constant-flow perfused hindlimb of urethane-anesthetized rats. 3. Tonic influence of the cardiopulmonary vagal afferents was evaluated by examining the effects of vagotomy on hindlimb vascular resistance and on the gain of arterial baroreflex control of hindlimb vascular resistance. 4. The gain of the arterial baroreflex control of hindlimb vascular resistance in response to both phenylephrine and nitroprusside were not significantly different between SHR receiving high and normal salt diets, and between WKY receiving high and normal salt diets. 5. Vagotomy increased hindlimb vascular resistance in all four groups of rats. However the high salt diet than those in SHR on a normal salt diet but similar between the two groups of WKY. Vagotomy increased the slope of arterial baroreflex control of hindlimb vascular resistance in SHR receiving a normal salt diet and the two groups of WKY but not in SHR receiving a high salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of anesthesia on sympathetic nerve rhythm: power spectral analysis

It has been shown that central transduction of the input from arterial baroreceptors shows bandpass characteristics. Previous studies have demonstrated that anesthesia may affect the gain of arterial baroreflex control of sympathetic nerve activity, but whether anesthesia affects the frequency response of central transduction of the arterial baroreflex system is not known. We examined cardiac cycle-related oscillation of renal sympathetic nerve activity (RNA) in conscious ( n = 5) and α-chloralose-anesthetized ( n = 10) rabbits. Power spectra of arterial pressure and RNA were obtained at rest, after i.v. propranolol and after i.v. isoproterenol. At rest with a cardiac cycle at about 5 Hz, cardiac cycle-related oscillation of RNA was observed in conscious rabbits, but it was not present or markedly attenuated in anesthetized rabbits. As the cardiac cycle was slowed by propranolol in anesthetized rabbits, cardiac cycle-related oscillation of RNA gradually appeared. These results suggest that α-chloralose anesthesia in rabbits narrowed the bandpass region of the central baroreflex system so that the baroreceptor input at a high frequency (above 5 Hz) was no longer transduced into RNA.

Alpha-ANP alters reflex control of lumbar and renal sympathetic nerve activity and heart rate.

This study examined the effects of synthetic alpha-rat atrial natriuretic peptide (alpha-rANP) on arterial pressure (AP), heart rate (HR), and renal and lumbar sympathetic nerve activity (SNA) in rats with intact arterial baroreceptors before and after bilateral vagotomy and in those with sinoaortic denervation before and after vagotomy. In intact rats, alpha-rANP decreased AP, which was accompanied by the decrease in renal SNA ad HR and no change in lumbar SNA. In contrast, the increase in lumbar SNA and HR occurred during hypotension caused by nitroglycerin. In rats with intact arterial baroreceptors and vagi sectioned, renal and lumbar SNA and HR did not change during hypotension with alpha-rANP. In addition, alpha-rANP did not alter the gain of arterial baroreflex control of lumbar SNA in these rats. In rats with sinoaortic denervation, alpha-rANP decreased HR and renal and lumbar SNA before vagotomy but did not change them after vagotomy. These results suggest, first, that alpha-rANP activates vagal afferents and thereby inhibits renal and lumbar SNA and HR and, second, that alpha-rANP may reset arterial baroreflex control of SNA and HR to a lower pressure range.

Altered control of hindlimb vascular resistance by vagal afferents in spontaneously hypertensive rats. Difference in the early and late stage of hypertension.

The aim of this study was to examine whether control of vascular resistance by vagal afferents is altered in the early as well as late stage of hypertension. We examined the effects of vagotomy on hindlimb vascular resistance as well as on arterial baroreflex control of hindlimb vascular resistance in spontaneously hypertensive rats and Wistar-Kyoto rats, 12 and 35 weeks old. Vagotomy in rats with the intact arterial baroreceptors increased hindlimb vascular resistance in all four groups. Hindlimb vascular responses to graded sympathetic nerve stimulation were closely linear up to 6 Hz in all groups, and the slope of the response was approximately 1.4 times steeper in spontaneously hypertensive than in Wistar-Kyoto rats, in both the young and old groups. The increase in hindlimb vascular resistance after vagotomy normalized by the slope of the response to sympathetic nerve stimulation was greater in young spontaneously hypertensive rats than in young Wistar-Kyoto rats, but was less in old spontaneously hypertensive rats than in old Wistar-Kyoto rats. Vagotomy increased the gain of arterial baroreflex control of hindlimb vascular resistance in young spontaneously hypertensive rats, and in two groups of Wistar-Kyoto rats, but not in old spontaneously hypertensive rats. The percent increase in the gain of arterial baroreflex control of hindlimb vascular resistance after vagotomy tended to be greater in young spontaneously hypertensive than in young Wistar-Kyoto rats, but was less in old spontaneously hypertensive than in old Wistar-Kyoto rats. Central venous pressure and left ventricular end-diastolic pressure were higher in spontaneously hypertensive than in Wistar-Kyoto rats in both young and old groups. Left atrial distensibility assessed by obtaining the atrial pressure-volume relationship was comparable between young spontaneously hypertensive and young Wistar-Kyoto rats, but was less in old spontaneously hypertensive than in old Wistar-Kyoto rats. These results indicate that vagal afferents exert tonic inhibition on control of hindlimb vascular resistance in spontaneously hypertensive as well as in Wistar-Kyoto rats, and that tonic inhibitory influence of vagal afferents on control of hindlimb vascular resistance is altered in spontaneously hypertensive rats, augmented in young, but attenuated in old, spontaneously hypertensive rats, compared with that in age-matched Wistar-Kyoto rats. It is considered that altered control of vascular resistance by vagal afferents in spontaneously hypertensive rats may result from changes in vagal afferent activity.