Resetting Of Baroreceptors Research Articles

Control of Blood Pressure Following Carotid Artery Stenting: Is it Baroreceptor Resetting? (P1.3-058)

Control of Blood Pressure Following Carotid Artery Stenting: Is it Baroreceptor Resetting? (P1.3-058)

Assessment of left ventricular ejection force and sympathetic skin response in normotensive and hypertensive subjects: A double-blind observational comparative case–control study

BackgroundPathophysiology of essential hypertension remains obscure. Correlation among ventricular ejection force, sympathetic activity, and hypertension is less clearly narrated in hypertensive subjects. Aims and objectivesTo assess correlation among ventricular ejection force, sympathetic activity, and hypertension in hypertensive subjects, and to be compared with normotensive subjects. MethodsThis is a case–control study to assess left ventricular ejection force (LVEF) and sympathetic skin response, in normotensive (group 1; control), and hypertensive subjects (group 2; cases). 100 cases were selected. Subjects having stages 1 and 2 hypertension were categorized in groups 2A and 2B, respectively. LVEF was calculated by using echocardiography observing aortic acceleration time (AT) and peak systolic velocity. Comparison among groups was done by using one-way ANOVA. ResultsBoth groups were comparable. In group 2, 60 cases had stage 1 hypertension and 40 had stage 2 hypertension. Significantly short AT and significantly high LVEF were found in hypertension (groups 2A and 2B) (p<0.0001). Sympathetic activity was high in group 2A (p<0.0001). Stroke volume (SV) was high in group 2B (p<0.0001). ConclusionStage 1 hypertension is a stage of increased sympathetic activity, leading to increased LVEF and hypertension (resetting of baroreceptors); stage 2 hypertension is a stage of normal sympathetic activity, increased LVEF, increased SV, and hypertension (possibly a stage of shift of renal equilibrium curve/renal output curve and blood pressure to a newer level).

Carotid Baroreceptor Stimulation for the Treatment of Resistant Hypertension

Interventional activation of the carotid baroreflex has been an appealing idea for the management of resistant hypertension for several decades, yet its clinical application remained elusive and a goal for the future. It is only recently that the profound understanding of the complex anatomy and pathophysiology of the circuit, combined with the accumulation of relevant experimental and clinical data both in animals and in humans, has allowed the development of a more effective and well-promising approach. Indeed, current data support a sustained over a transient reduction of blood pressure through the resetting of baroreceptors, and technical deficits have been minimized with a subsequent recession of adverse events. In addition, clinical outcomes from the application of a new implantable device (Rheos) that induces carotid baroreceptor stimulation point towards a safe and effective blood pressure reduction, but longer experience is needed before its integration in the everyday clinical practice. While accumulating evidence indicates that carotid baroreceptor stimulation exerts its benefits beyond blood pressure reduction, further research is necessary to assess the spectrum of beneficial effects and evaluate potential hazards, before the extraction of secure conclusions.

Role of cardiopulmonary and carotid sinus baroreceptors in regulating renal sympathetic nerve activity during water immersion in conscious dogs

The aim of the present study was to investigate how loading of cardiopulmonary baroreceptors induced by water immersion (WI) modifies baroreflex control of renal sympathetic nerve activity (RSNA) in conscious dogs. Nine dogs were chronically instrumented for measuring carotid sinus nerve activity (CSNA), RSNA, carotid arterial (Pca), and central venous (Pcv) pressures. The stimulus-response relationships of Pca-CSNA and Pca-RSNA were determined simultaneously in the same dog by changing Pca using rapid intravenous infusions vasoactive drugs during pre-WI and WI. WI increased central venous pressure significantly (P < 0.05) by 10.4 mmHg. WI shifted the Pca-RSNA curve acutely leftward compared with the pre-WI period, which was associated with significant (P < 0.05) decreases in the saturation pressure by 39.0 mmHg and operating range by 43.1 mmHg. WI relocated the operating pressure to near the saturation pressure, where the gain was low. The Pca-CSNA curve obtained during WI was identical to that obtained during pre-WI period. These results suggest that the shift in baroreflex control of RSNA could be attributed to the inhibitory influence of the cardiopulmonary mechanoreceptor loading and not by the resetting of carotid baroreceptors per se.

The NTS and integration of cardiovascular control during exercise in normotensive and hypertensive individuals

Due to upward resetting of baroreceptors, tachycardia coexists with increased pressure during dynamic exercise. This review critically evaluates current knowledge of proposed mechanisms to explain the continuous resetting of baroreflex control of heart rate and sympathetic nerve activity during and after exercise and exercise training. Of interest is the exercise-induced upward resetting that occurs in hypertensive and normotensive individuals. Accumulated evidence indicates that not only somatosensory afferents, but also inputs from central command projecting to the nucleus tractus solitarius (NTS) in the dorsal brainstem may mediate inhibition of excitatory neurotransmission on barosensitive neurons. Specific coordinated activation of vasopressinergic and oxytocinergic projections to the NTS is essential to tonically maintain baroreflex sensitivity and to adjust heart rate and cardiac output to circulatory demand at rest and during exercise in both sedentary and trained individuals. These findings reinforce the paramount importance of the NTS in integration of cardiovascular control during exercise.

RESETTING OF AORTIC BARORECEPTORS IN RESPONSE TO HYPOTENSION DOES NOT ALTER GAIN SENSITIVITY

1. In chronic hypertension, the baroreceptors reset to hypertensive levels with a decrease in gain sensitivity, but only a few studies have evaluated baroreceptor resetting during chronic hypotension and, under these conditions, no consistent information is available concerning changes in baroreceptor gain sensitivity. Therefore, in the present study, the aortic baroreceptor function curve and the baroreflex control of heart rate (HR) were evaluated in chronic hypotension produced by myocardial infarction (MI) with no heart failure. 2. Aortic baroreceptor function curves were studied in anaesthetized three groups of rats: (i) MI-7, six rats 7 days after MI; (ii) MI-30, nine rats 30 days after MI; and (iii) five control animals (SHAM). The pressure-nerve activity relationship was measured during rapid changes in blood pressure by integrating the whole-nerve activity of the baroreceptors in a computerized beat-to-beat analysis. 3. Both long-term periods (7 or 30 days) of hypotension were accompanied by complete resetting of the baroreceptor in rats (the leftward displacement of the baroreceptor curve matched the decrease in blood pressure). Moreover, the resetting of the baroreceptor function curve was not accompanied by changes in gain sensitivity (1.47, 1.64 and 1.67%/mmHg for SHAM, MI-7 and MI-30 groups, respectively) and the baroreflex control of HR was normal comparing SHAM and MI-30 groups (bradycardic 1.62 +/- 0.18 vs 1.99 +/- 0.52 b.p.m./mmHg, respectively; tachycardic 3.6 +/- 0.5 vs 4.1 +/- 0.4 b.p.m./mmHg for, respectively). 4. The data indicate that the resetting of baroreceptors in chronic hypotension is stable and is not accompanied by changes in gain sensitivity, as observed in hypertension. This may account for the normal baroreflex control of HR observed in non-anaesthetized rats.

Baroreceptors, baroreceptor unloading, and the long-term control of blood pressure

Whether arterial baroreceptors play a role in setting the long-term level of mean arterial pressure (MAP) has been debated for more than 75 years. Because baroreceptor input is reciprocally related to efferent sympathetic nerve activity (SNA), it is obvious that baroreceptor unloading would cause an increase in MAP. Experimental proof of concept is evident acutely after baroreceptor denervation. Chronically, however, baroreceptor denervation is associated with highly variable changes in MAP but not sustained hypertension. The ability of baroreceptors to buffer imposed increases in MAP appears limited by a process termed "resetting," in which the threshold to fire shifts in the direction of the pressure change and if the pressure elevation is maintained, it leads to a rightward shift in the relationship between baroreceptor firing and MAP. The most common hypothesis linking baroreceptors to changes in MAP proposes that reduced vascular distensibility in baroreceptive areas would cause reduced firing at the same pulsatile pressure and, thus, reflexively increase SNA. This review focuses on effects of baroreceptor denervation in the regulation of MAP in human subjects compared with animal studies; the relationship between vascular compliance, MAP, and baroreceptor resetting; and, finally, the effect of chronic baroreceptor unloading on the regulation of MAP.

Arterial baroreflexes can determine long‐termblood pressure

Arterial baroreflexes can determine long‐termblood pressure

Baroreceptors and the long-term control of blood pressure.

The current consensus is that arterial baroreceptors are vitally important in the short term (seconds to minutes) control of mean arterial pressure (MAP) but are unimportant in determining the long-term level of MAP. The latter statement is based primarily on two observations: first, that baroreceptors rapidly reset to the prevailing level of MAP and second, that total baroreceptor denervation has no lasting effect on the average daily MAP, although the variability of MAP is increased dramatically. However, recent studies in intact experimental animals have produced results that suggest baroreceptor resetting may not be as rapid or complete as previously thought. Furthermore, reconsideration of the responses to baroreceptor denervation suggest that the condition may accurately represent responses to short-term baroreceptor unloading but not long-term unloading. Results obtained using a new model of chronic baroreceptor unloading indicate that the condition results in a sustained increase in MAP. These results strongly suggest that the role of baroreceptors in the long term control of MAP needs to be revisited.

Corrigendum

CORRIGENDACorrigendumPublished Online:01 May 2004https://doi.org/10.1152/ajpregu.00102.2004Original articleMoreSectionsPDF (22 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Volume 55, January 2004 Pages R1-R12: Malpas SC. “What sets the long-term level of sympathetic nerve activity: is there a role for arterial baroreceptors? (https://doi.org/10.1152/ajpregu.00496.2003). Reference 6 should read as follows: Andresen MC and Yang M. Arterial baroreceptor resetting: contributions of chronic and acute processes. Clin Exp Pharmacol Physiol Suppl 15: 19-30, 1989.This article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformationRelated articlesWhat sets the long-term level of sympathetic nerve activity: is there a role for arterial baroreceptors? 01 Jan 2004American Journal of Physiology-Regulatory, Integrative and Comparative Physiology More from this issue > Volume 286Issue 5May 2004Pages R975-R975 Copyright & PermissionsCopyright © 2004 the American Physiological Societyhttps://doi.org/10.1152/ajpregu.00102.2004History Published online 1 May 2004 Published in print 1 May 2004 Metrics

Cardiovascular deconditioning in microgravity: some possible countermeasures.

Microgravity is an extreme environment inducing relevant adaptive changes in the human body, especially after prolonged periods of exposure. Since the early sixties, numerous studies on the effects of microgravity, during manned Space flights, have produced an increasing amount of information concerning its physiological effects, globally defined "deconditioning". Microgravity deconditioning of the cardiovascular system (CVD) is briefly reviewed. It consists of: (1) a decrease of circulating blood and interstitial fluid volumes, (2) a decrease of arterial blood diastolic pressure, (3) a decrease of ventricular stroke volume, (4) a decrease of the estimated left ventricular mass and (5) resetting of the carotid baroreceptors. The negative effects of microgravity deconditioning manifest themselves mostly upon the reentry to Earth. They consist mainly of: (1) dizziness, (2) increased heart rate and heart palpitations, (3) an inability to assume the standing position (orthostatic intolerance), (4) pre-syncopal feelings due to postural stress and (5) reduced exercise capacity. To avoid these drawbacks several countermeasures have been proposed; they will be briefly mentioned with emphasis on the "Twin Bikes System" (TBS). This consists of two coupled bicycles operated by astronauts and counter-rotating along the inner wall of a cylindrical Space module, thus generating a centrifugal force vector, mimicking gravity.

Afferent baroreceptor discharge in pregnant rats.

The baroreflex function curve is shifted to lower operating pressures, efferent sympathoexcitatory responses are attenuated, and sympathoinhibitory responses are potentiated in pregnant compared with virgin rats. It has been proposed that during pregnancy, elevated levels of 3 alpha-hydroxy-dihydroprogesterone (3 alpha-OH-DHP), a major metabolite of progesterone, may contribute to this difference, because acute intravenous administration of 3 alpha-OH-DHP to virgin female rats mimics the effects of pregnancy on the baroreflex. To determine whether changes in the afferent limb might contribute to these baroreflex responses, the effects of pregnancy and 3 alpha-OH-DHP on aortic depressor nerve activity were assessed in the current study. Baroreceptor discharge curves were obtained in Inactin-anesthetized rats by recording aortic nerve activity during ramp increases and decreases in mean arterial pressure (MAP) [intravenous phenylephrine and nitroprusside infusion] before [(control, C) 15 min (E1), and 30 min (E2) after 3 alpha-OH-DHP (220 microg/kg bolus + 22 microg x kg(-1) x min(-1) infusion iv)]. Baseline blood pressure was significantly lower in pregnant (109 +/- 4.4 mmHg) compared with virgin (122 +/- 2.8 mmHg) rats. The only significant difference in the baroreceptor discharge curves was a decrease in curve midpoint in pregnant rats (virgin = 140 +/- 2.7 vs. pregnant = 124 +/- 3.6 mmHg). 3 alpha-OH-DHP had no effect on afferent baroreceptor discharge curves in either virgin or pregnant groups. These results suggest that pressure-dependent baroreceptor resetting may contribute to a shift in the baroreflex curve to lower operating pressures, but cannot completely explain differences in baroreflex function between virgin and pregnant animals.

Morphology of aortic depressor nerve myelinated fibers in normotensive Wistar–Kyoto and spontaneously hypertensive rats

Reports on the morphology of the baroreceptor terminal of spontaneously hypertensive rats (SHR) did not demonstrate any difference when compared to the axonal terminal of normotensive rats. Although several studies reporting baroreceptor terminal and blood vessel wall morphology have been carried out to better understand the baroreceptor function and resetting to hypertensive levels, there are no reports examining the morphology of the fibers of the aortic depressor nerve (ADN) in hypertensive models. Therefore, the objective of the present study was to investigate the morphological aspects of SHR ADN compared to Wistar–Kyoto (WKY) rats. Before the morphologic study, the nerves were isolated and the pressure–nerve activity curve was determined for each ADN. SHR exhibited an increase in the threshold pressure for baroreceptor activation, a rightward shift in the pressure–nerve activity curve with decreases in slope and maximum activity. Semithin (0.3 to 0.5 μm thick) sections of the proximal (close to the nodose ganglion) and distal (close to the aortic arch) segments of the ADN were analyzed by light microscopy. A morphometric study of the nerve fascicles and myelinated fibers was performed. Comparison between proximal and distal segments of the two strains revealed that the ADN of WKY rats were consistently larger. All morphometric parameters studied in myelinated fibers and their respective axons were smaller in SHR. The area of the myelin sheath was comparatively larger in WKY rats. These data show morphologic differences between the ADN of SHR and WKY rats, which may explain, at least in part, the decreased slope and maximum activity of the pressure–nerve activity curve observed with the baroreceptor resetting in SHR.

Absence of early resetting of coronary baroreceptors in anaesthetized dogs.

1. Both carotid and aortic arch baroreceptors have been shown to reset after as little as 20 min exposure to a different conditioning pressure; the mid-point of the stimulus-response curve is displaced towards the conditioning pressure. 2. Coronary baroreceptors operate over much lower pressures and induce slower reflex vasoconstriction than the other baroreceptors and this investigation was designed to determine whether their resetting characteristics are also different. 3. In chloralose anaesthetized dogs, a perfusion circuit allowed independent control of pressures distending carotid, aortic and coronary baroreceptors. Stimulus-response curves were obtained for carotid and coronary baroreceptors after maintaining the distending pressure at 60 or 180 mmHg for 20 min. 4. Neither the magnitude of the responses nor the baroreceptor pressure corresponding to 50 % of the response (BP50) of the coronary curves was changed by the conditioning regime. In contrast, conditioning carotid baroreceptors with the same regime produced significant shifts in the BP50 towards the conditioning pressure. 5. No changes were obtained after conditioning the coronary baroreceptors at 60 or 120 mmHg for 40 min. 6. These results confirm early resetting of carotid baroreceptors but show that coronary baroreceptors do not reset over a period of at least 40 min.

Renal sympathetic nerve activity in mice: comparison between mice and rats and between normal and endothelin-1 deficient mice

Recently generated knockout mice with disrupted genes encoding endothelin (ET)-1 showed an elevation of arterial blood pressure (AP) and supplied an evidence for intrinsic ET-1 as one of the physiological regulators of systemic AP. Little is yet known, however, why deficiency of ET-1, which was originally found as a potent vasoconstrictor, led to higher AP in these mice. To address this apparent paradox, we first developed a method to measure renal sympathetic nerve activity (RSNA) in mice using rats as reference and successively compared it between normal and ET-1 deficient mice. RSNA was successfully recorded in urethane-anesthetized and artificially ventilated mice by a slight modification of the method used for rats. At basal condition, mean AP (MAP) and RSNA in ET-1 deficient mice (105±2 mmHg and 9.71±1.49 μVs, n=20) were significantly higher than those in wild-type mice (96±2 mmHg and 5.07±0.70 μVs, n=25). Basal heart rate (HR) and baroreflex-control of HR was not significantly different between the two. On the other hand, resting RSNA, RSNA range, and maximum RSNA were significantly greater in ET-1 deficient mice, and thus MAP-RSNA relationship was upwards reset. Hypoxia-induced increase in RSNA was not different between ET-1 deficient (73.4±9.4%) and wild-type mice (91.2±12.0%), while hypercapnia-induced one was significantly attenuated in ET-1 deficient mice (18.8±3.6 vs. 39.1±5.2% at 10% CO 2). These results indicate that endogenous ET-1 participates in the central chemoreception of CO 2 and reflex control of the RSNA. Baroreceptor resetting and normally preserved hypoxia-induced chemoreflex may explain a part of the elevation of AP in ET-1 deficient mice.

13 Baroreflex Regulation of Blood Pressure during Dynamic Exercise

From the work of Potts et al. Papelier et al. and Shi et al. it is readily apparent that the arterial (aortic and carotid) baroreflexes are reset to function at the prevailing ABP of exercise. The blood pressure of exercise is the result of the hemodynamic (cardiac output and TPR) responses, which appear to be regulated by two redundant neural control systems, "Central Command" and the "exercise pressor reflex". Central Command is a feed-forward neural control system that operates in parallel with the neural regulation of the locomotor system and appears to establish the hemodynamic response to exercise. Within the central nervous system it appears that the HLR may be the operational site for Central Command. Specific neural sites within the HLR have been demonstrated in animals to be active during exercise. With the advent of positron emission tomography (PET) and single-photon emission computed tomography (SPECT), the anatomical areas of the human brain related to Central Command are being mapped. It also appears that the Nucleus Tractus Solitarius and the ventrolateral medulla may serve as an integrating site as they receive neural information from the working muscles via the group III/IV muscle afferents as well as from higher brain centers. This anatomical site within the CNS is now the focus of many investigations in which arterial baroreflex function, Central Command and the "exercise pressor reflex" appear to demonstrate inhibitory or facilitatory interaction. The concept of whether Central Command is the prime mover in the resetting of the arterial baroreceptors to function at the exercising ABP or whether the resetting is an integration of the "exercise pressor reflex" information with that of Central Command is now under intense investigation. However, it would be justified to conclude, from the data of Bevegard and Shepherd, Dicarlo and Bishop, Potts et al., and Papelier et al. that the act of exercise results in the resetting of the arterial baroreflex. In addition, if, as we have proposed, the cardiopulmonary baroreceptors primarily monitors and reflexly regulates cardiac filling volume, it would seem from the data of Mack et al. and Potts et al. that the cardiopulmonary baroreceptor is also reset at the beginning of exercise. Therefore, investigations of the neural mechanisms of regulation involving Central Command and cardiopulmonary afferents, similar to those being undertaken for the arterial baroreflex, need to be established.

Viscoelastic mechanisms of aortic baroreceptor resetting to hypotension and to hypertension.

Viscoelastic and electrophysiological mechanisms have been implicated in the resetting of baroreceptors in hypertension, but resetting in response to hypotension has been less studied. To evaluate the temporal relationship between viscoelastic mechanisms and acute resetting, we examined the "in vivo" behavior of aortic caliber and aortic baroreceptor activity during step changes in pressure. Fifteen-minute hemorrhage in Wistar rats produced stable hypotension (30 mmHg) and viscoelastic contraction (111 +/- 14.2 microns systolic caliber; P < 0.01). Integrated aortic activity fell to 19.8 +/- 3.9% of control (P < 0.001) after 3 s of hypotension but recovered to 64 +/- 4.1% 15 min later (P < 0.01 from 3 s). Recovery of baroreceptor activity was linearly correlated to viscoelastic contraction (r = 0.963; P < 0.0001). Thirty-minute phenylephrine infusion (1.0-4.0 micrograms/min) produced stable hypertension (30 mmHg) and viscoelastic dilation (211 +/- 37.0 microns systolic caliber). Integrated aortic activity increased to 218.0 +/- 18% of control values (P < 0.001) 30 s after hypertension and was reduced to 164.0 +/- 12.0% (P < 0.001 from 3 s) within 30 min. Reduction of baroreceptor activity correlated linearly with viscoelastic relaxation (r = 0.963; P < 0.0001). The results indicate that in the in vivo rat aorta, viscoelastic mechanisms parallel and may contribute to the baroreceptor resetting during hypotension and hypertension.

Stimulation of endogenous nitric oxide pathway by L-arginine reduces declamp mortality and attenuates hypertension associated with aortic cross-clamp-induced hindlimb ischemia in rats.

We tested the hypotheses that maintaining the activity of nitric oxide by L-arginine infusion would counteract the release of an endogenous nitric oxide synthase inhibitor, improve survival, and decrease intraoperative hypertension after infrarenal aortic cross-clamp surgery. Hindlimb ischemia was generated by infrarenal aortic cross-clamping and tying of the left femoral artery for 5 hours in rats with bilateral femoral and sciatic nerves cut. Mean blood pressure significantly increased during the 5-hour ischemic period in ischemic rats (no drug treatment). Baroreceptor function was inhibited in ischemic rats assessed by intravenous dose response to phenylephrine and nitroprusside after 5 hours of ischemia, suggesting baroreceptor resetting. In ischemic rats infused with L-arginine the intraoperative hypertension was prevented during the 5-hour period, suggesting that this hypertension may be mediated by nitric oxide inhibition. The rates of survival and arrhythmias 2 hours after declamping were 50% in ischemic rats and 100% in ischemic rats treated with N omega-nitro-L-arginine (a nitric oxide synthase inhibitor) 10 minutes before declamping. In ischemic rats infused with L-arginine the survival rate was significantly increased to 100% and the arrhythmic rate was inhibited. We conclude that L-arginine prevents hypertension during cross-clamping and decreases the mortality rate and arrhythmias after declamping by maintaining nitric oxide synthesis. These results suggest that humoral factors released from the ischemic hindlimb may inhibit endogenous nitric oxide production, thus contributing to intraoperative hypertension, arrhythmias, and high mortality rate after aortic cross-clamp surgery.

Structural versus functional modulation of the arterial baroreflex.

Structural changes in large arteries are often considered the predominant mechanism responsible for decreased baroreflex sensitivity and baroreceptor resetting in hypertension, atherosclerosis, and aging. Recent work has demonstrated that "functional" mechanisms, both at the level of the peripheral sensory endings and within the central nervous system, contribute significantly to altered baroreflex responses. We have conducted both reductive studies of mechanoelectrical transduction in cultured baroreceptor neurons and integrative studies with in vivo recordings of the activity of baroreceptor afferent fibers and efferent sympathetic nerves. Results suggest that the primary mechanism of mechanical activation of baroreceptor neurons involves opening of stretch-activated ion channels susceptible to blockade by gadolinium. Baroreceptor nerve activity is modulated by the activity of potassium channels and the sodium-potassium pump and by paracrine factors, including prostacyclin, oxygen free radicals, and factors released from aggregating platelets. Endothelial dysfunction and altered release of these paracrine factors contribute significantly to the decreased baroreceptor sensitivity in hypertension and atherosclerosis. The central mediation of the baroreflex depends on the pulse phasic pattern of afferent baroreceptor discharge. Baroreflex-mediated inhibition of sympathetic nerve activity is well maintained during pulse phasic afferent activity. Continuous, nonphasic baroreceptor discharge or a rapid (> 1.5 Hz) pulse phasic discharge results in disinhibition of sympathetic activity. This disinhibition during continuous baroreceptor input is exaggerated with aging. Thus, a defect in central mediation of the baroreflex may be a major cause of the impaired baroreflex and sympathoexcitation in the elderly. In summary, functional neural mechanisms, in addition to structural vascular changes, contribute importantly to altered baroreflex responses in normal and pathophysiological states.(ABSTRACT TRUNCATED AT 250 WORDS)

Pressor and subpressor angiotensin II administration two experimental models of hypertension

Administered dose is an important determinant of the type of hypertension produced by angiotensin II. With chronic administration of pressor doses, there is salt and water retention and expansion of extracellular fluid volume, and the pressure-natriuresis curve is shifted to higher pressures. Important compensatory mechanisms, including resetting of baroreceptors, de novo synthesis of vasodilator prostaglandins, and atrial natriuretic factor release, are triggered by the acute rise of blood pressure. Histologic evidence for vascular injury confounds the interpretation of findings. When angiotensin II is administered in initially subpressor doses, the rise of blood pressure is gradual, there are no detectable changes in salt and water balance, and compensatory mechanisms do not seem to be activated. Autopotentiation of pressor and vasoconstrictor responses by angiotensin II is the characteristic feature of the early stages of hypertension induced by small doses of angiotensin II. Trophic stimulation of vascular tissue, in particular restructuring of extracellular matrix, precedes and may, therefore, be the mechanism responsible for the hemodynamic changes. The pressor and subpressor models of angiotensin II-induced hypertension draw attention to the relative importance of renal and extrarenal mechanisms in the pathogenesis of hypertension. The long-term administration of initially subpressor doses of angiotensin II mimics the development of human hypertension to a greater extent than does the administration of pressor doses.