TIME COURSE OF CHANGES IN BARORECEPTOR REFLEX CONTROL OF HEART RATE IN CONSCIOUS SHR AND WKY: CONTRIBUTION OF THE CARDIAC VAGUS AND SYMPATHETIC NERVES

1. The aim of this study was to assess the vagal and sympathetic nerve contribution to the relationship between mean arterial pressure (MAP) and heart rate (HR) at 6, 9, 14 and 20 weeks of age in conscious Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) with methoxamine- and nitroprusside-induced steady-state changes in blood pressure. 2. MAP increased with age in both strains but was 17-23% higher in SHR. 3. By contrast baroreflex parameters (HR range: difference between upper and lower HR plateaus, and gain: average slope between inflection points of the logistic MAP-HR relationship) decreased with age in SHR but increased in WKY. 4. After methylatropine, no differences in the cardiac sympathetic baroreflex range or gain parameters were observed between strains or ages. 5. It was concluded that older SHR have normal sympathetic but reduced vagal capacity to control HR in response to changes in MAP, but that this deficit was not dependent on the absolute level of blood pressure. 6. Because the differences were confined to one effector, SHR may have different central rather than arterial baroreceptor afferent mechanisms.     

CARDIAC BAROREFLEXES AND HYPERTENSION

1. The role of cardiac reflexes in baroreflex control mechanisms and the changes that occur in chronic hypertension is reviewed. The rapid resetting properties of the arterial baroreceptors ensures its role in short-term rather than long-term control of blood pressure. 2. In hypertensive humans and animals, the baroreceptor-heart rate reflex has diminished sensitivity due mainly to reduced maximum capacity of the cardiac vagal component rather than a change to the sympathetic. 3. The development of this vagal deficit in spontaneously hypertensive rats (SHR) coincides with the onset of cardiac hypertrophy rather than vascular hypertrophy. A combination of chronic perindopril treatment regimens in young and older SHR showed that the vagal deficit was better correlated with the degree of cardiac hypertrophy than with other variables such as blood pressure, hypertension or indices of vascular hypertrophy. Similar results have been shown for renovascular hypertension in rats. 4. The bradycardia produced by electrical stimulation of the vagus in urethane anaesthetized young SHR was enhanced compared to Wistar-Kyoto rats (WKY) while responses observed in adult SHR and WKY were similar, suggesting that the vagal deficit in hypertensive rats is not due to a defect in the efferent arm of the baroreflex. 5. The association of the vagal deficit with cardiac hypertrophy, but not with the vagal efferent pathways, suggests an important role for cardiac afferents in hypertension in mediating the baroreflex deficit. 6. A diminished baroreflex and also a reduced heart rate variability is an independent risk factor for sudden death following myocardial infarction. Thus, antihypertensive therapy, which more effectively reduces cardiac hypertrophy, should have a desirable effect on baroreceptor reflexes and therefore in reducing blood pressure variability.     

Effects of intracisternal and intravenous alpha-methyldopa and clonidine on haemodynamics and baroreceptor--heart rate reflex properties in conscious rabbits

We determined the doses of intracisternal (i.c.) and intravenous (i.v.) clonidine and alpha-methyldopa (alpha-MD) that produced near-maximal falls in mean arterial pressure (MAP) in conscious rabbits. We then studied the haemodynamic mechanisms underlying the fall in MAP and changes in the properties of the baroreceptor-heart rate reflex. Intracisternal and intravenous administration of both drugs lowered MAP by approximately 25% of control, and the fall was about half due to the reduction in cardiac output and about half due to a fall in total peripheral resistance. Baroreceptor-heart rate reflex properties were studied by transiently inflating perivascular balloons to alter blood pressure and by deriving sigmoid curves relating MAP to heart period (HP, pulse interval). Both drugs produced very similar vagal facilitation during transient rises in MAP when given by the i.c. and i.v. routes; HP range (between upper and lower plateaus) increased to 145% of control, and gain rose to 190%. The effects of i.c. administration of both drugs on the cardiac sympathetic component of the baroreflex were studied in methscopolamine-treated rabbits. Clonidine produced more pronounced suppression of HP range and gain, while alpha-MD had little effect. These differences between drugs were still present with much larger i.c. doses. Our findings suggest that both drugs influence resting haemodynamics and the vagal component of the baroreflex through similar effects on the central autonomic pathways. But there are some differences in their central actions on cardiac sympathetic motoneurons.     

Cardiovascular functions of brain serotonergic neurons in the rabbit as analysed from the acute and chronic effects of 5,6-dihydroxytryptamine

The effects of intracisternal (i.c.) 5,6-dihydroxytryptamine (5,6-DHT) or creatinine sulphate vehicle on mean arterial pressure (MAP), heart rate, and baroreceptor-heart rate and nasopharyngeal reflex properties were studied in conscious rabbits. For the baroreflex we derived sigmoid MAP-heart period (HP) curves, and for the nasopharyngeal reflex we measured apnea time, rise in HP, and delta MAP. The acute effects occurring over the first few hours in intact and decerebrate rabbits included: (a) tachycardia and a decrease in baroreflex HP range and gain, which were mediated through bulbar or spinal pathways influencing vagal motoneurons; (b) a transient early rise in MAP through a bulbar or spinal pathway and a late suprapontine rise in MAP; and (c) shorter apnea time, less bradycardia, and less well-maintained MAP during nasopharyngeal stimulation. By day 14, when spinal cord serotonin was depleted by 70%, resting MAP and heart rate had recovered, HP range and gain had risen above initial control, but nasopharyngeal apnea time and bradycardia were still reduced. Some of the acute responses were due to synaptic release of serotonin (5HT); since the tachycardia and late component of the pressor response were blocked by pretreatment with i.c. methysergide, the acute changes in baroreflex parameters were opposite to the chronic changes, and a second injection of 5,6-DHT failed to produce these changes. On the other hand, the acute and chronic nasopharyngeal responses were similar, suggesting that the former were due to neuronal block and not 5HT release. These findings indicate that central serotonergic neurons inhibit cardiac vagal activity, increase blood pressure through both suprapontine and bulbar or spinal pathways, and are involved in the nasopharyngeal reflex.     

EFFECTS OF HIGH SALT INTAKE ON CONTROL OF HINDLIMB VASCULAR RESISTANCE BY ARTERIAL BROREFLEX 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 magnitude of the increase in hindlimb vascular resistance was less in SHR on a 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. 6. These results suggest that a high salt diet attenuates the inhibitory influence of vagal afferents on the control of vascular resistance in SHR but not in WKY, while the arterial baroreflex control of vascular resistance is preserved during high salt diet in both SHR and WKY.     

Differential effects of central and peripheral desipramine on sympathoadrenal function and heart rate in conscious rabbits.

The effects of the tricyclic antidepressant, desipramine, on the baroreflex regulation of renal sympathetic nerve activity (SNA) and heart rate (HR), the nasopharyngeal reflex, plasma epinephrine and blood pressure (BP) were studied in conscious rabbits. Renal SNA and HR were recorded during slow ramp changes in mean arterial pressure (MAP) and during inhalation of cigarette smoke. Intracisternal (i.c.) and intravenous (i.v.) drug administration were compared, using doses which produced similar total central nervous system (CNS) concentrations. After a brief sympathoexcitation, i.c. desipramine inhibited renal SNA and MAP and increased plasma adrenaline and HR. The renal sympathetic baroreflex was substantially attenuated, with reflex range and gain reduced by 46 and 31%, respectively, but the cardiac baroreflex and nasopharyngeal reflex were affected minimally. Sixty-four percent of the desipramine remaining in the brain was concentrated in the medulla oblongata and spinalis; levels in cortex, thalamus, midbrain, lower spinal cord, and peripheral tissues were minimal. Treatment with i.v. desipramine decreased renal SNA and increased HR without altering MAP or epinephrine release. There was a slight attenuation of the nasopharyngeal reflex, a slight baroreceptor-independent reduction in renal SNA at most MAP levels, and an augmentation of the cardiac baroreflex. The drug was uniformly distributed throughout the CNS; only 20% of the centrally accumulated dose was in the medulla. Thus, i.c. desipramine produces a differentiated pattern of sympathoadrenal effects, probably by increasing norepinephrine (NE) concentrations at several sites within the medulla. The effects of i.v. desipramine were different, owing to poorer access to the medulla and the consequences of peripheral neuronal uptake blockade, which may include a modest inhibition at the sympathetic ganglia and an excitation at cardiac and vasoconstrictor neuroeffector junctions.     

Changes in autonomic activity and baroreflex sensitivity with the hypertension process and age in rats

1. Autonomic activity and baroreflex sensitivity (BRS) were compared in age-matched conscious groups of Wistar Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP). 2. Male WKY rats, SHR and SHRSP aged 4-30 weeks were used. Autonomic activity and BRS were estimated by power spectral and cross-spectral analysis of systolic blood pressure (SBP) and SBP-SBP (SS) interval fluctuations, respectively. 3. The time-course of heart rate (HR), SBP, the amplitude of the low-frequency component of SBP fluctuation (SBP-LF; prazosin-sensitive index) and the amplitude of the high-frequency component of the SS interval fluctuation (SS-HF; atropine-sensitive index) consisted of two periods. In the first period (up to 10 or 15 weeks of age), BP, SBP-LF and SS-HF increased with age. The order of SBP-LF was SHRSP > SHR > WKY rats throughout this period. During the second period, BP was sustained at certain levels in all strains, but changes in SBP-LF and SS-HF with age were different among strains. In particular, in SHRSP, SBP-LF markedly decreased with age after 10 weeks. Baroreflex sensitivity in WKY rats increased gradually with age, whereas the BRS in SHR and SHRSP decreased before 6 weeks of age and remained lower than that in WKY rats. 4. In conclusion, the present study shows that both prazosin-sensitive and atropine-sensitive indices are associated with the elevation of BP in all strains studied. However, hypertension after 15 weeks of age in SHRSP is sustained despite a paradoxical reduction in sympathetic activity with an abnormal control of BRS. Therefore, the contribution of autonomic activity to hypertension may be discussed separately as a developmental period and a sustained period.     

Central endogenous histamine modulates sympathetic outflow through H3 receptors in the conscious rabbit

1. This study examined the role of histamine H(3) receptors in vagal and sympathetic autonomic reflexes in the conscious rabbit, and in rabbit and guinea-pig isolated right atria. 2. The baroreceptor-heart rate reflex (baroreflex), Bezold-Jarisch-like and nasopharyngeal reflexes were assessed after these treatments (i.v.; with H(1) and H(2) receptor block): (i) vehicle (saline; n=11); (ii) H(3) receptor agonist, (R)-alpha-methylhistamine (R-alpha-MH) 100 micro g kg(-1)+100 micro g kg(-1) h(-1) (n=9); (iii) H(3) receptor antagonist, thioperamide 1 mg kg(-1)+1 mg kg(-1) h(-1) (n=11); (iv) R-alpha-MH and thioperamide (n=6); and (v) H(2) and H(3) antagonist, burimamide 6.3 mg kg(-1)+6.3 mg kg(-1) h(-1) (n=4). 3. R-alpha-MH caused a thioperamide-sensitive fall in mean arterial pressure (MAP) of 8+/-1 mmHg and tachycardia of 18+/-2 bpm (P<0.0005). Burimamide was without effect, however thioperamide elicited an increase in MAP of 4+/-1 mmHg (P<0.01), but no change in heart rate (HR). 4. R-alpha-MH caused a 44% decrease in the average gain of the baroreflex (P=0.0001); this effect was antagonised by thioperamide. Thioperamide caused a parallel rightward shift in the barocurve with an increase in MAP of 5 mmHg (P<0.05). Burimamide had no effect on the baroreflex. The vagally mediated bradycardia elicited by the Bezold-Jarisch and nasopharyngeal reflexes was unaffected by H(3) receptor ligand administration. 5. R-alpha-MH (相似文献   

The effect of ketanserin on cardiovascular reflexes in conscious normotensive and spontaneously hypertensive rats

The effect of ketanserin (3 mg/kg i.v.) on the baroreceptor heart rate reflex and the Bezold-Jarisch reflex was examined in conscious Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In the control situation (before ketanserin treatment), reflex bradycardia in response to phenylephrine (baroreflex) and phenyldiguanide (Bezold-Jarisch reflex) were impaired in SHR as compared with WKY, while reflex tachycardia in response to nitroprusside was similar in the two groups. However, after ketanserin administration in SHR, there was a reversal of the baroreflex-mediated tachycardia in response to nitroprusside into a bradycardic response. The nitroprusside-induced bradycardia was not caused by the release of 5-HT stimulating chemosensitive vagal afferents since the 5-HT3 receptor antagonist MDL 72222 did not block this response. In the same SHR, the Bezold-Jarisch reflex evoked by phenyldiguanide and the phenylephrine-induced bradycardia were potentiated by ketanserin. All the above effects of ketanserin were less evident in the WKY. Ketanserin did not alter vagal efferent function in anaesthetized SHR since it did not affect bradycardia induced by electrical stimulation of the vagus nerve. Therefore, it is suggested that ketanserin has sensitised cardiac vagal afferent mechanisms in SHR, which led to a normalization of reflex bradycardic function to a level normally observed in conscious normotensive WKY (i.e. prior to ketanserin treatment).     

Renal and cardiac sympathetic baroreflexes in hypertensive rabbits

1. The purpose of the present study was to assess the changes to renal sympathetic nerve activity (RSNA) baroreflexes during the development of hypertension after renal clipping in conscious rabbits. 2. Rabbits were fitted with a clip on the right renal artery or underwent a sham operation under halothane anaesthesia. A recording electrode was implanted on the left renal nerve 1 week before the experiment, 3 or 6 weeks after the initial operation. During the experiment, drug-induced ramp rises and falls in mean arterial pressure (MAP) were used to produce RSNA and heart rate (HR) baroreflex curves. The RSNA for each experiment was calibrated against maximum RSNA evoked by stimulation of baroreceptor-independent trigeminal afferents. 3. Mean arterial pressure was 20 and 36% higher 3 and 6 weeks after clip implantation, respectively. Renal sympathetic nerve activity baroreflex curves were reset rightwards accordingly, but the shape of the RSNA curves was differentially affected. 4. At both hypertensive periods, MAP-HR baroreflex gain was markedly reduced due to a reduction in curvature. The HR baroreflex range was increased. The RSNA baroreflex gain was reduced at 3 weeks, which was due to a 35% lower RSNA baroreflex range, but was similar to sham animals at 6 weeks. 5. The results show that, in established two kidney, one clip hypertension in rabbits, the sympathetic baroreflex is relatively well preserved but sensitivity of cardiac baroreflexes is attenuated. Therefore, the short-term inhibition of RSNA baroreflexes is not related to the level of blood pressure or the development of secondary changes, such as cardiac or vascular hypertrophy, but may be related to circulating angiotensin, which is known to increase at this time.     

Role of cardiac hypertrophy in reducing the sensitivity of cardiopulmonary reflex control of renal sympathetic nerve activity in spontaneously hypertensive rats

The gain of the volume-sensitive cardiopulmonary reflex (VSCR) is impaired in spontaneously hypertensive rats (SHR). Sensitivity of VSCR control of efferent renal sympathetic nerve activity (RSNA) in SHR is restored when cardiac hypertrophy and hypertension are reduced by enalapril treatment. The present study investigated which of these two parameters, cardiac hypertrophy or hypertension, has more influence on the impairment of VSCR control of RSNA in SHR. Rats (SHR or Wistar-Kyoto (WKY) rats) were treated with enalapril (10 mg/kg per day; SHRE and WKYE groups, respectively) or hydralazine (5 mg/kg per day; SHRH and WKYH groups, respectively) mixed in their food for 1 month. Control SHR and WKY rats were fed a normal diet. After the treatment regimen, the VSCR was evaluated by determining the decrease in RSNA elicited by acute isotonic saline volume expansion. Mean arterial pressure (MAP) was assessed via an intrafemural catheter and cardiac hypertrophy was determined by the left ventricular (LV) weight/bodyweight (BW) ratio. Afferent baroceptor nerve activity (BNA) was also evaluated during volume expansion to verify participation of the baroreflex. Volume expansion produced an attenuated renal sympathoinhibitory response in SHR compared with WKY rats. Enalapril treatment restored the volume expansion-induced decrease in RSNA in SHRE (-41 +/- 8%) compared with WKY rats (-44 +/- 3%). Although both enalapril and hydralazine treatment reduced MAP in SHR (P < 0.01; 126 +/- 5, 133 +/- 6 and 160 +/- 6 mmHg in SHRE, SHRH and SHR, respectively), hydralazine did not restore the sensitivity of VSCR control of RSNA in SHRH. Spontaneously hypertensive rats with established hypertension had a higher LV/BW ratio compared with WKY rats (3.22 +/- 0.14 vs 1.98 +/- 0.06 mg/g, respectively; P < 0.01). Enalapril reduced the LV/BW ratio in SHRE (2.30 +/- 0.07 mg/g; P < 0.01). Although hydralazine reduced LV hypertrophy, there was a weaker reduction in SHRH (2.68 +/- 0.04 mg/g; P < 0.05) compared with SHRE. There was no statistically significant difference among the WKY rat, WKYE and WKYH groups (P > 0.05). There was no change in afferent BNA during volume expansion in normal or hypertensive animals. Taken together, these results indicate that the impairment of VSCR control of RSNA in the SHR model of hypertension correlates better with the magnitude of cardiac hypertrophy than the level of arterial pressure.     

Centrally produced neuronal nitric oxide in the control of baroreceptor reflex sensitivity and blood pressure in normotensive and spontaneously hypertensive rats

We studied the effect of chronic nitric oxide synthase (NOS) blockade in the brain on mean arterial pressure [MAP (mmHg)], heart rate [HR (bpm)] and baroreceptor reflex sensitivity [BRS (mean slope: bpm/mmHg)] in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Intracerebroventricular (i.c.v.) infusion of the nonselective NOS inhibitor N-Nitro-L-arginine-methylester (L-NAME) (50 microg/kg per day, 11-12 days) increased MAP in WKY and SHR (125+/-2.1 vs 118+/-1.1 controls, P<0.01 and 179+/-3.59 vs 156+/-4.0 controls, P<0.001, respectively) without affecting HR. In L-NAME-treated WKY, BRS to bradycardia was suppressed (-0.79+/-0.09 vs -1.76+/-0.17 controls, P=0.001), whereas in SHR, L-NAME did not affect BRS to bradycardia. BRS to tachycardia remained unaffected in either strain. In WKY, 7-nitroindazole (7-NI x Na+) (34 microg i.c.v./kg per day, 11-12 days), a selective nNOS inhibitor, did not affect MAP or HR, but BRS to bradycardia and tachycardia was decreased (-0.37+/-0.20 vs -0.97+/-0.41 controls, P<0.01 and -1.78+/-0.20 vs -2.52+/-0.40 controls, P=0.05, respectively). In SHR, the same dose of 7-NI x Na+ increased resting MAP (171+/-5.00 vs 150+/-7.00 controls, P<0.05) without affecting HR or BRS to bradycardia or tachycardia. Thus in WKY, BRS to acute changes in systemic blood pressure (BP) is regulated by NO produced by nNOS in the brain, serving as a neurotransmitter in sympathetic and parasympathetic efferent pathways. In SHR, systemic BP is regulated in part by NO released by the type I NOS isoenzyme in the brain.     

Effects of clonidine on the baroreceptor-heart rate reflex and on single aortic baroreceptor fibre discharge

The effects of clonidine (Catapres^®) on the baroreceptor-heart rate reflex were studied in unanaesthetized rabbits, and its action on single aortic baroreceptor fibre discharge was examined under anaesthesia. Intravenous clonidine (bolus 2.5 to 10 μg/kg + infusion of 0.25 to 1.5 μg/kg/min) altered the mean arterial pressure (MAP) — heart period (HP; pulse interval) curve, reducing median blood pressure and increasing the gain and heart period range (HPR). At low dose increased HPR by enhancing both vagal excitation and sympathetic inhibition of HP during a rise in MAP, compared with control conditions. At high i.v. dose of drug sympathetic inhibition was complete even at low MAP, and HPR increased due to a rise in vagal output to 4–6 times control. Lateral ventricle injections of 0.5 to 1.5 μg/kg of clonidine altered MAP - HP curve parameters in a similar manner as i.v. infusion. High dose of clonidine i.v. enhanced single aortic baroreceptor fibre discharge at a given MAP in anaesthetized animals, but there was no effect at low dose. Clonidine alters heart rate mainly through its direct central action on the baroreceptor pathways; at high dose these effects are reinforced by peripheral baroreceptor resetting. Clonidine has only slight effects on cardiac motoneurones not receiving baroreceptor projections.     

VASOPRESSIN COMPENSATES FOR ACUTE LOSS OF SYMPATHETIC PRESSOR TONE IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The aim of this study was to examine the pressor response of vasopressin (AVP) to an acute fall in blood pressure induced by ganglion blockade. 2. Aortic catheters were implanted in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), normotensive Wistar-Kyoto (WKY), black-hooded Wistar (BHW) and Sprague-Dawley (SD) rats, aged 5–7 weeks and 7–9 months, for direct measurement of mean arterial pressure (MAP) under conscious, resting conditions. The ganglion blocking agent pentolinium was administered intra-arterially, followed by an AVP receptor antagonist specific for the pressor effect of AVP. The basal level of MAP attained with each drug was recorded. 3. In the adult SHR and SHRSP with established hypertension, acute ganglion blockade caused MAP to fall to a similar extent as in WKY, suggesting that the level of sympathetic pressor tone was similar in all three strains. Administration of the AVP antagonist alone did not affect resting MAP. During ganglion blockade, however, it caused a further reduction of MAP in WKY, SHR and SHRSP, the magnitude of which was greater in the hypertensive strains. After both drugs, the total fall in MAP and the residual MAP were significantly greater in the hypertensive rats. 4. In young rats, AVP had little effect on MAP, even during ganglion blockade. The residual level of MAP after both drugs was greater in the hypertensive strains. 5. The extent to which AVP can compensate for an acute fall in MAP increases with age and the development of hypertension. This tends to mask the loss of sympathetic mediated pressor tone after ganglion blockade. By preventing this compensation we have shown that the sympathetically mediated component of blood pressure is elevated in SHRSP with established hypertension.     

Baroreflex deficit blunts exercise training‐induced cardiovascular and autonomic adaptations in hypertensive rats

1. Baroreceptors regulate moment‐to‐moment blood pressure (BP) variations, but their long‐term effect on the cardiovascular system remains unclear. Baroreceptor deficit accompanying hypertension contributes to increased BP variability (BPV) and sympathetic activity, whereas exercise training has been associated with an improvement in these baroreflex‐mediated changes. The aim of the present study was to evaluate the autonomic, haemodynamic and cardiac morphofunctional effects of long‐term sinoaortic baroreceptor denervation (SAD) in trained and sedentary spontaneously hypertensive rats (SHR). 2. Rats were subjected to SAD or sham surgery and were then further divided into sedentary and trained groups. Exercise training was performed on a treadmill (five times per week, 50–70% maximal running speed). All groups were studied after 10 weeks. 3. Sinoaortic baroreceptor denervation in SHR had no effect on basal heart rate (HR) or BP, but did augment BPV, impairing the cardiac function associated with increased cardiac hypertrophy and collagen deposition. Exercise training reduced BP and HR, re‐established baroreflex sensitivity and improved both HR variability and BPV. However, SAD in trained SHR blunted all these improvements. Moreover, the systolic and diastolic hypertensive dysfunction, reduced left ventricular chamber diameter and increased cardiac collagen deposition seen in SHR were improved after the training protocol. These benefits were attenuated in trained SAD SHR. 4. In conclusion, the present study has demonstrated that the arterial baroreflex mediates cardiac disturbances associated with hypertension and is crucial for the beneficial cardiovascular morphofunctional and autonomic adaptations induced by chronic exercise in hypertension.     

INFLUENCE OF CARDIAC AFFERENTS ON TIME-DEPENDENT CHANGES IN THE RENAL SYMPATHETIC BAROREFLEX OF CONSCIOUS RABBITS

1. The stability of the renal sympathetic baroreflex and nasopharyngeal reflex, and the role of cardiac sensory receptors, was studied in conscious rabbits over a 5 h experimental period. 2. Renal sympathetic nerve activity (SNA) was recorded during (i) slow ramp changes in mean arterial pressure (MAP) of 1-2 mmHg/s induced by inflating perivascular balloon cuffs, and (ii) the inhalation of cigarette smoke. Experiments were repeated in other rabbits after blocking cardiac afferents with 5% intrapericardial procaine. 3. Baroreflex responses to the first two caval cuff inflations of the day were significantly greater than subsequent responses. After this, triplicate sets of reflex curves were relatively stable during a 2 h period in the morning. When the experiment was repeated in the afternoon, there was a significant attenuation of baroreflex range and a small fall in resting renal SNA which were abolished by pericardial procaine. 4. Changes in baroreflex properties were minimal when the reflex was assessed only twice, at the beginning and end of a 5 h period. No change was seen in the nasopharyngeal reflex whether the rabbits had been subjected to few or to many cuff inflations. 5. We conclude that time dependent changes can occur in the renal sympathetic baroreflex of conscious rabbits which must be allowed for by appropriate protocol design. These include increasing inhibitory influences from cardiac sensory receptors in experimental situations requiring multiple reflex estimations.     

Upregulation of tachykinin NK-1 and NK-3 receptor binding sites in the spinal cord of spontaneously hypertensive rat: impact on the autonomic control of blood pressure

1 Effects of intrathecally (i.t.) injected tachykinin NK-1 and -3 receptor agonists and antagonists were measured on mean arterial blood pressure (MAP) and heart rate (HR) in awake unrestrained spontaneously hypertensive rats (SHR,15-week-old) and age-matched Wistar Kyoto rats (WKY). Quantitative in vitro autoradiography was also performed on the lower thoracic spinal cord of both strains and Wistar rats using specific radioligands for NK-1 receptor ([(125)I]HPP[Arg(3),Sar(9),Met(O(2))(11)]SP (3-11)) and NK-3 receptor ([(125)I]HPP-Asp-Asp-Phe-N-MePhe-Gly-Leu-Met-NH(2)). 2 The NK-1 agonist [Sar(9),Met(O(2))(11)]SP (650 and 6500 pmol) decreased MAP and increased HR in WKY. The fall in MAP was blunted in SHR and substituted by increases in MAP (65-6500 pmol) and more sustained tachycardia. The NK-3 agonist senktide (6.5-65 pmol) evoked marked increases in MAP and HR (SHR>WKY), yet this response was rapidly desensitized. Cardiovascular effects of [Sar(9),Met(O(2))(11)]SP (650 pmol) and senktide (6.5 pmol) were selectively blocked by the prior i.t. injection of LY303870 (NK-1 antagonist, 65 nmol) and SB235375 (NK-3 antagonist, 6.5 nmol), respectively. Antagonists had no direct effect on MAP and HR in both strains. 3 Densities of NK-1 and -3 receptor binding sites were significantly increased in all laminae of the spinal cord in SHR when compared to control WKY and Wistar rats. The dissociation constant was however not affected in SHR for both NK-1 (K(d)=2.5 nM) and NK-3 (K(d)=5 nM) receptors. 4 Data highlight an upregulation of NK-1 and -3 receptor binding sites in the thoracic spinal cord of SHR that may contribute to the hypersensitivity of the pressor response to agonists and to the greater sympathetic activity seen in this model of arterial hypertension.     

Possible involvement of an impaired baroreflex mechanism but not the renin-angiotensin system and vasopressin in the enhanced pressor responsiveness to physostigmine in spontaneously hypertensive rats

Effects of physostigmine on heart rate, mean arterial pressure (MAP), plasma renin concentration (PRC) and vasopressin (AVP) release were investigated in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Physostigmine (100 micrograms/kg, i.a.) produced a greater and prolonged hypertensive response in the SHR than in the WKY. Heart rate was increased by physostigmine in SHR rats while it was unchanged in the WKY. PRC was unchanged or even slightly decreased in these animals when MAP was increased by physostigmine. An AVP pressor antagonist did not attenuate the pressor and cardiac effects of physostigmine in these animals. These data indicate that an impaired baroreflex mechanism or a different mode of sympathetic neuronal activation by physostigmine through the central mechanism appears to be contributory, at least in part, to the enhanced pressor responsiveness in the SHR. The renin-angiotensin system and AVP do not appear to be involved in the enhanced pressor responsiveness to physostigmine in SHR rats.     

''Steady-state'' properties of the baroreceptor-heart rate reflex in essential hypertension in man

SUMMARY 1. Rises and falls in mean arterial (MAP) and pulse (PP) pressures from the resting value were evoked by intravenous injections of phenylephrine and glyceryl trinitrate, and were related to the reflexly evoked changes in heart period (HP; pulse interval).
2. The steady-state properties of the baroreceptor-heart rate reflex were examined by deriving MAP-HP curves in a group of twenty-three healthy normotensive subjects, and in two groups of sixteen and eight subjects with essential hypertension of different severity. Each group was subdivided into two subgroups according to age: (i) 18–30 years; (ii) 33–57 years. The MAP-HP curves are sigmoid and each is characterized by its median blood pressure (BP₅₀), average gain (1) and heart period range (HPR).
3. In a given age group, the curves are 'reset' about a higher BP₅₀ with increasing severity of hypertension. There is progressive reduction in HPR (to 80–55% of normotensive HPR) due to lowering of the upper HP plateau, which probably indicates impairment of function of the vagal component of the reflex. In three out of four hypertensive groups, is also significantly reduced to between 60 and 30% of of normotensive subjects of the same age.
4. The effect of age on the curve parameters is independent of the effects due to hypertension. For a given MAP, and HPR are lower in older than in younger subjects.     

Adrenomedullin in the rostral ventrolateral medulla inhibits baroreflex control of heart rate: a role for protein kinase A

1 The rostral ventrolateral medulla (RVLM) is an essential vasomotor center in the brainstem which participates in maintaining resting levels of arterial pressure and for regulating baroreflex activity. We have demonstrated that microinjections of adrenomedullin (ADM), a vasoactive neuropeptide, into the RVLM cause increased resting mean arterial pressure (MAP) and heart rate (HR). However, the effect of ADM on baroreflex function remains unclear. 2 The purposes of the present study were to investigate the effect of ADM in the RVLM on the regulation of baroreflex activity and to identify the underlying mechanisms. Baroreflex curves were generated with intravenous injections of multiple doses of phenylephrine and nitroprusside. The upper and lower plateaus, reflex range, MAP at the midpoint of HR range (MAP(50)), and gain were evaluated before and after various microinjections were made into the RVLM of urethane-anesthetized rats. 3 Microinjections of ADM decreased the upper plateau, reflex range, and gain, and increased MAP(50), indicating that ADM in the RVLM impairs baroreflex function. 4 ADM(22-52), a putative ADM receptor antagonist, significantly increased the baroreflex gain and upper plateau, demonstrating that endogenous ADM tonically inhibits the baroreflex. Coinjections of ADM(22-52) with ADM blocked the ADM-induced baroreflex responses. 5 ADM's effect was abolished with H-89, a protein kinase A (PKA) inhibitor. 6 Our results show that ADM in the RVLM exerts an inhibitory effect on baroreflex activity via an ADM receptor-mediated mechanism, and that activation of PKA is involved in this event.