Baroreflex In Hypertension Research Articles

The Baroreflex in Hypertension.

Hypertension is a complex syndrome that increases the risk of developing other medical comorbidities and interacts with other medical conditions to increase the risk of target end-organ damage such as cardiovascular disease, stroke, and renal disease. Hypertension remains under-recognized and poorly controlled in the USA and worldwide. In some patients, hypertension is resistant to optimal medical therapy. Over the last few decades, there has been an increasing understanding of the role of the sympathetic nervous system in the development and maintenance of hypertension. This update reviews the physiology and role of the sympathetic nervous system in hypertension and pharmacological and interventional treatments directed at nervous system involvement in secondary hypertension.

Vagus nerve morphology in elderly spontaneously hypertensive rats (728.23)

Aging affects peripheral nerve function and regeneration in experimental models but few literature reports deal with animals aged one year or more. The vagus nerve is an important branch of the efferent arm of the baroreflex heading to the heart. In adult spontaneously hypertensive rats (SHR), the vagus nerve morphology was compared between genders [1] and no differences were found. However, the effects of aging associated to hypertension were not yet investigated for this nerve. Male SHR aged 20 and 50 weeks had their arterial pressure (AP) and heart rate (HR) recorded by a computerized system. The rats were then systemically perfused with a fixative solution and had their cervical vagi nerves prepared for light microscopy. Proximal and distal segments of the left and right vagi nerves were evaluated for morphometric parameters including fascicle area and diameter. Comparisons were made between sides and segments on the same age as well as between ages. Differences were considered significant when p<0.05. SHR aged 50 weeks were heavier than 20‐week old animals, with no differences on the AP and HR averages. Body weight differences were followed by fascicular area and diameter results, as 50‐week old animals have larger vagus nerve fascicles compared to 20‐week old animals. Also, 50‐week old animals presented a clear reduction of the number of endoneural vessels compared to younger animals. This results deserves further investigations. Our data provide a morphological basis for further studies involving functional investigations of the efferent arm of the baroreflex in hypertension associated with ageing.[1] Alcântara et al. Brain Res 1197:170, 2008.Grant Funding Source: FAPESP, CAPES, CNPq and FAEPA

Impaired baroreflex sensitivity as a potential marker of cardiovascular risk in hypertension

Impaired baroreflex sensitivity as a potential marker of cardiovascular risk in hypertension

Morphology and morphometry of the vagus nerve in male and female spontaneously hypertensive rats

The vagus nerve is an important component of the efferent arm of the baroreflex. Blood pressure levels as well as baroreflex control of circulation are significantly different in male and female spontaneously hypertensive rats (SHR). We proposed to investigate the morphometric differences between genders using the vagus nerve of SHR. Adult animals (20 weeks old) were anesthetized and had their arterial pressure (AP) and heart rate (HR) recorded by a computerized system. The rats were then systemically perfused with a fixative solution and had their cervical vagi nerves prepared for light microscopy. Proximal and distal segments of the left and right vagi nerves were evaluated for morphometric parameters including fascicle area and diameter, myelinated fiber number, density, area and diameter. Comparisons were made between sides and segments on the same gender as well as between genders. Differences were considered significant when p < 0.05. Male SHR had significantly higher AP and HR. Morphometric data showed no differences between the same levels of both sides and between segments on the same side for male and female rats. In addition, no significant morphometric differences were observed when genders were compared. This is the first description of vagus nerve morphometry in SHR indicating that gender differences in AP and HR cannot be attributed to dissimilarities in vagal innervation of the heart. These data provide a morphological basis for further studies involving functional investigations of the efferent arm of the baroreflex in hypertension.

Baroreflexes in Hypertension

To date, most studies investigating baroreflexes in hypertension have been performed either by recording baroreflex afferents or by denervating them. In the current issue of Hypertension , Lohmeier et al1 present data on the effects of chronic carotid sinus stimulation (CSS) in hypertensive animals. Striking differences were observed during CSS in dogs with angiotensin II (Ang II)-induced hypertension as compared with control conditions. In line with a previous study,2 baroreflex activation by CSS significantly reduced blood pressure during control. In contrast, the hypotensive effect was markedly attenuated in Ang II hypertensive dogs. This observation fits very well with today’s understanding of baroreflexes in several forms of hypertension. Remarkably, it is still not fully understood how the autonomic nervous system acts in hypertension, although the issue dates back to the very beginnings of research on cardiovascular reflexes. During that era, it …

The sympathetic nervous system and hypertension: recent developments.

A major hypothesisfor the development of hypertension is that abnormal renal excretory function is critical for the initiation, development, and maintenance of primary hypertension.1 The renal body fluid feedback mechanism couples the long-term regulation of arterial pressure to extracellular volume (sodium and water) homeostasis via pressure natriuresis, whereby the kidneys respond to changes in arterial pressure by altering urinary sodium and water excretion. The obligatory requirement for maintenance of sodium and water balance by the kidneys is believed to be primary in the long-term control of arterial pressure. An increase in arterial pressure (via increases in total peripheral resistance or cardiac output or both) leads to an increased urinary sodium and water excretion via the pressure natriuresis mechanism, with consequent reduction in blood volume until arterial pressure is returned to normal. Thus, factors that decrease renal excretory function and disrupt the maintenance of sodium and water balance by the kidneys lead to an increase in arterial pressure, which is required to reestablish and maintain sodium and water balance. Based on computer modeling studies, a long-term increase in arterial pressure can only occur if there is a chronic and sustained decrease in renal excretory function. Increased renal sympathetic nerve activity (RSNA) is known to be a factor capable of decreasing renal excretory function.2,3 The renal effects of increased RSNA include increased renal tubular sodium reabsorption leading to renal sodium retention; decreased renal blood flow and glomerular filtration rate with renal vasoconstriction and increased renal vascular resistance; and increased renin release leading to angiotensin II production. Each of these renal functional alterations can decrease renal excretory function. The role of increased RSNA as being a critically important factor contributing to this renal excretory dysfunction in hypertension is strengthened by the fact that increased RSNA has been identified in hypertensive human …

The sympathetic nervous system and baroreflexes in hypertension and hypotension.

Blood pressure and blood volume are closely regulated by the interrelated actions of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Reflex vasoconstriction caused by parallel SNS and RAAS activation is modulated by two interactive negative feedback systems called baroreflex. The aortic-carotid baroreflex systems respond to momentary changes in systolic blood pressure, adjusting the degree of SNS-dependent peripheral vasoconstriction and cardiac output to allow maintenance of a relatively constant perfusion pressure. Cardiopulmonary baroreflexes respond to momentary changes in cardiac filling, adjusting the degree of peripheral venoconstriction and venous return to maintain cardiac preload and stroke volume. Under normal conditions, each baroreflex system exhibits a degree of tonic negative feedback so that it can alter SNS output immediately, providing counterregulatory increases or decreases in pressure or volume to maintain homeostasis. The SNS is inappropriately active in obesity and hypertension and plays a causal or permissive role in all forms of chronic hypertension. If the negative feedback control exerted by the baroreflexes over the SNS and renin-angiotensin-aldosterone system (RAAS) were perfect, chronic hypertension would not occur. Activity of the baroreflexes, however, is chronically altered by maladaptive changes such as cardiac and vascular fibrosis and hypertrophy. Long-term increases in SNS and RAAS activity also exert ongoing deleterious effects on the heart and vasculature by directly facilitating further cardiac hypertrophy and arterial stiffening. These effects appear to contribute to a vicious cycle of chronic hypertension and target organ damage. Other syndromes of abnormal blood pressure (BP) control, including orthostatic hypotension and baroreflex failure are examples of abnormal baroreflex activity and SNS control.

Cardiac baroreflex in hypertension: role of the heart and angiotensin II.

Sigmoid logistic function curves provide a powerful means of characterizing the baroreceptor-heart rate reflex. In hypertension the operating range of the reflex is reset in the direction of the elevated resting BP; this can be accounted by rapid resetting of the threshold of the arterial baroreceptors. In addition, there is a deficit in the vagal component of the heart rate (HR) range. Reduction in gain occurs in moderate/severe hypertension, but may be absent in young primary hypertensives. All the changes are reversible, and reversibility of HR range and gain is related to reducing left ventricular hypertrophy or central blood volume rather than to reduction in BP. High plasma angiotensin II can further accentuate the vagal deficit. An input-output model has been developed from comparison of perivascular cuff and drug methods for eliciting the reflex, which place different loads on the heart; the greater load changes simulate many of the alterations in reflex properties observed in hypertension. We conclude that during changes in vasomotor tone in normal animals, about 70% of the drive for the cardiac baroreflex comes from arterial baroreceptors and about 30% from low threshold cardio-pulmonary baroreceptors. In hypertension, the vagal deficit in HR range is due to afferent interactions involving arterial and low and high threshold cardio-pulmonary baroreceptors.

Clonidine improves central attenuation of the baroreflex in spontaneously hypertensive rats.

To determine whether clonidine can improve the central alteration of the baroreflex in SHR, the centrally cut end of the aortic depressor nerve was electrically stimulated in SHR with intravenously administered clonidine. Aortic depressor nerve (ADN) stimulation elicited depressor and sympatho-inhibitory responses in a frequency-dependent manner in WKY and SHR. These responses were significantly smaller in SHR than in WKY. The attenuated depressor and sympatho-inhibitory responses to ADN stimulation in SHR were restored following i.v. injections of clonidine, although the drug did not affect the responses to ADN stimulations in WKY. These findings suggest that clonidine can improve central attenuation of the baroreflex in hypertension.

Baroreceptor resetting and other determinants of baroreflex properties in hypertension.

1. Rapid resetting of the arterial baroreceptor threshold in the normal circulation extends the pressure range over which baroreflexes operate at high gain. During sustained falls and rises in resting blood pressure (BP), changes in reflex threshold may be greater or less than those of the receptors, through interactions with other sources of afferent drive (e.g. cardiac baroreceptors). In chronic hypertension the magnitude of the reflex resetting again corresponds to that of the arterial baroreceptors, probably because of the resetting of the threshold of the cardiac receptors. 2. 'Baroreflexes' in intact animals are compound reflexes with input from both arterial and non-arterial baroreceptors (e.g. cardiac/pulmonary baroreceptors). The steady-state responses can be characterized by BP-autonomic output function curves, which are often sigmoidal, with a well-defined effector response range and gain. Both sets of input contribute to the high gain component close to resting, with the arterial baroreceptors the major source of reflex drive; the non-arterial baroreceptors also contribute over this part of the reflex and their role increases considerably at high and low BP. 3. In chronic mild/moderate hypertension the changes in baroreflex properties are similar to those of moderate acute rises in BP or in cardiac load; heart rate range of the vagal component of the cardiac baroreflex is depressed, gain is slightly enhanced and the Valsalva-total peripheral resistance (TPR) reflex is unaltered. In severe hypertension: (i) vagal heart rate range and gain are further depressed; and (ii) there is depression of the Valsalva-TPR reflex, much as observed in constrictor reflexes during acute hypertension in normal animals. Circulatory disturbances produce engagement of non-arterial baroreceptors more readily in hypertensives than in normotensives; depression of baroreflexes in hypertension is due partly to enhanced drive from these receptors and partly due to reduction in the gain of the arterial baroreceptors. 4. The reflex vagal depression and that of neural constrictor reflexes can be considered as important homeostatic mechanisms that limit the effects of circulatory perturbations on cardiac filling pressures and on excessive rises in vascular resistance.

Diminished baroreflex sensitivity in high blood pressure.

Sudden intravenous injections of small amounts of angiotensin or phenylephrine were given to 30 subjects to produce modest, brief increases in directly measured systemic arterial pressure. A plot of each systolic pressure against the second succeeding cardiac cycle length produced a linear distribution, the slope of which was expressed as the millisecond increase in cycle length per mm Hg rise in systolic pressure. The slope is an index of baroreflex sensitivity and was found to have an average value of 12.8 in 18 subjects without hypertension and 2.8 in 12 others with hypertension. When all results were pooled, there was an inverse relationship between the resting mean arterial pressure and slope of the baroreflex regression lines. The findings demonstrate reduced sensitivity of the baroreflexes in hypertension, with respect to control of heart rate. A distinction is made between this change in sensitivity and simple resetting of the reflex.