Paul I. Korner

The renal sympathetic baroreflex in the rabbit. Arterial and cardiac baroreceptor influences, resetting, and effect of anesthesia.

Curves relating renal sympathetic nerve activity and mean arterial pressure were derived in conscious rabbits during ramp changes in mean arterial pressure, elicited by perivascular balloon inflation. The renal sympathetic nerve activity-mean arterial pressure relationship consisted of a high-gain sigmoidal region about resting, where renal sympathetic nerve activity rose or fell in response to moderate falls and rises of mean arterial pressure. With larger pressure rises, renal sympathetic nerve activity first fell to a lower plateau and then reversed at even higher mean arterial pressure. When mean arterial pressure was lowered below resting, renal sympathetic nerve activity rose to an upper plateau and then reversed abruptly toward resting at low mean arterial pressure. Both arterial and cardiac baroreceptors exerted substantial inhibitory influences on renal sympathetic nerve activity at all pressure levels. These effects appeared additive over the central high gain region of the curve, but beyond this region there were non-additive interactions. The latter were affected considerably by alfathesin anesthesia. In other experiments, we studied the effects of sustained alterations in resting mean arterial pressure induced by infusing nitroprusside and phenylephrine, which produced rapid resetting of the renal baroreflex. The latter could be accounted for, in part, by resetting of the threshold of the arterial baroreceptors and in part by contributions from other afferents, probably the cardiac receptors. During resetting associated with nitroprusside-induced falls in resting blood pressure, high-gain reflex adjustments in renal sympathetic nerve activity to moderate changes in mean arterial pressure were preserved, but during resetting associated with phenylephrine-induced rises in resting mean mean arterial pressure, the resting renal sympathetic nerve activity lay on the lower curve plateau, resulting in reduction in the apparent gain of the reflex renal sympathetic nerve activity response to moderate changes in mean arterial pressure.

‘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).

Central Nervous System Control of Baroreceptor Reflexes in the Rabbit

Aortic and inferior vena caval balloons were used to alter mean arterial blood pressure, pulse pressure (PP), and right atrial pressure (RAP) in unanesthetized rabbits and to reflexly evoke changes in heart period (pulse interval). Curves relating mean arterial blood pressure to heart period were compared in different groups of rabbits at similar ΔPP and ΔRAP. Median blood pressure (BP50), average gain (G), and heart period range (maximum to minimum heart period) were calculated from the S-shaped curves. The reflex was evoked from arterial baroreceptors and probably from cardiac and pulmonary baroreceptors. Curves relating mean arterial blood pressure and heart period differed with regard to BP50 and G in sham-operated, thalamic, and pontine rabbits, indicating that suprabulbar centers normally play a role in the reflex. Curves from sham-operated and pontine rabbits treated with atropine also differed, suggesting suprabulbar control of sympathetic effectors. In intact rabbits, forebrain and diencephalic centers caused vagal and sympathetic effectors to respond over the same arterial blood pressure range, but, in pontine rabbits, the effectors responded over dissimilar ranges. In intact rabbits, changes in mean arterial blood pressure evoked reciprocal and nearly equal changes in vagal and sympathetic effectors, but, in pontine rabbits, a given pressure change altered heart period predominantly through one effector. In sham-operated rabbits, vagal effects on heart period were lower by a constant amount at every level of mean arterial blood pressure than they were in pontine rabbits, suggesting that suprabulbar centers exerted a tonic inhibitory effect on vagal motoneurons not involved in the reflex.

Differential development of vascular and cardiac hypertrophy in genetic hypertension. Relation to sympathetic function.

We compared blood pressure, hlndquarter vascular resistance properties, left ventricular weight, and norepinephrine kinetics, in spontaneously hypertensive rats (SHR) and weight-matched normotensive Wistar-Kyoto (WKY) rats at 4, 9, 14, 20, 30, and 50 weeks of age- At 4 weeks, systolic and mean blood pressure measurements were the same in both strains, but the vascular resistance of the fully dilated hindquarter bed was significantly higher in SHR than in WKY rats, with a much larger difference during maximum constriction. Plots of resistance at maximum dilatation and at maximum constriction against body weight suggest that a component of the increase hi vascular muscle mass in SHR occurred in the neonatal period preceding hypertension followed by a later component related to the rise in blood pressure. By contrast, left ventricular hypertrophy was minimal at 4 weeks and most of its development paralleled the rise in blood pressure. Sympathetic activity, assessed by norepinephrine fractional rate constant, was higher in SHR than in WKY rats in the left ventricle and kidney through most of the period between 4 and 50 weeks, but was similar in both strains in the muscle bed. This pattern of sympathetic activity will accentuate hypertension once cardiac and vascular hypertrophy are fully established. In all regions, norepinephrine tissue concentration was higher in young SHR and could potentiate the trophic effects of growth factors in early vascular hypertrophy. We suggest that the initial (primary) component of vascular hypertrophy precedes the rise in blood pressure and may be critical in the pathogenesis of hypertension. Possible reasons for the short delay in the rise in blood pressure in young SHR, once the vascular “amplifier” has been established, include high vascularity, immaturity of smooth muscle, and delay in the development of left ventricular hypertrophy.

Rapid resetting of the aortic baroreceptors in the rabbit and its implications for short-term and longer term reflex control.

We studied the effects of sustained changes in resting mean arterial pressures (MAP) on arterial baroreceptor properties in anesthetized rabbits and on the baroreceptor-heart rate reflex in conscious animals. The rabbits had balloons implanted round their aorta and vena cava, for producing transient changes in MAP about the resting MAP. Aortic baroreceptor function curves were obtained at different resting MAP by relating balloon-induced changes in MAP to either (1) integrated aortic nerve activity or (2) unit baroreceptor activity. Any sustained change in resting MAP reset the unit function curves in the same direction within 15 minutes by altering their threshold without affecting gain. The effect was reversible and independent of starting pressure. It was the same whether resting MAP was altered by vasoactive drugs (nitroprusside, phenylephrine) or was changed by withdrawing or infusing blood in sympathetically blocked rabbits. We studied baroreflex function in conscious rabbits by deriving MAP-heart period (HP) curves at different resting MAP. Nitroprusside lowered baroreflex threshold for evoking bradycardia, whereas phenylephrine increased threshold. From our analysis, the resting MAP-mediated changes in receptor threshold accounted for the reflex threshold changes. Altered baroreceptor properties did not account for changes in baroreflex HP range produced by both drugs, and in reflex gain; these were probably due to afferent interactions in the CNS. Because of rapid arterial baroreceptor resetting, transient changes (of about 30 seconds or less) in MAP of moderate magnitude evoked normal reflex heart rate responses at each resting MAP. After changes in resting MAP sustained for 15 minutes or longer, reflex changes in resting heart rate were considerably smaller than in the absence of resetting. Therefore the arterial baroreceptors provide the baroreflex with a “floating” rather than a fixed set point, determined by the prevailing MAP.

Autonomic and Non-Autonomic Circulatory Components in Essential Hypertension in Man

The circulatory effects of blocking cardiac and peripheral autonomic effectors were studied in 32 subjects with established essential hypertension, and in 15 normotensives. The mean resting arterial pressure, heart rate and total peripheral resistance index (TPRI) were significantly higher in the hypertensives, but cardiac index was the same in both groups. In subjects with blocked cardiac effectors (atropine + beta-blocking drugs, i.v.) the sympathetic constrictor effects on TPRI were estimated from the changes after giving i.v. guanethidine + phentolamine. The autonomic component of TPRI was higher in hypertensives than in normotensives. The residual resistance after `total autonomic block (non-autonomic TPRI) was higher in hypertensives, accounting for 60 to 80% of the initial difference in resting TPRI between the two groups. With an increase in non-autonomic TPRI, the increased autonomic TPRI effect in hypertension is not necessarily due to increased sympathetic nerve activity. Vagal and cardiac sympathetic effects on heart rate were compared in the two groups. Each estimate was based on the average of the responses to the appropriate blocking drug (1) in subjects not previously given a blocking drug, and (2) in subjects with the other cardiac effector pathway already blocked. The higher heart rate in established hypertension was predominantly due to change in vagal rather than cardiac sympathetic effects.

The relative roles of the aortic and carotid sinus nerves in the rabbit in the control of respiration and circulation during arterial hypoxia and hypercapnia

1. The respiratory and circulatory effects of graded arterial hypoxia, alone or with superadded hypercapnia, were studied in four groups of unanaesthetized rabbits including normal animals and those with selective section of the aortic nerves, selective section of the carotid sinus nerves and section of both sets of nerves.

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

Abstract 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.

Integrative Reflex Control of Heart Rate in the Rabbit during Hypoxia and Hyperventilation

Baroreceptor mean arterial blood pressure-heart period curves were obtained for unanesthetized sham-operated, thalamic, or pontine rabbits at an arterial Po2 of 100 or 30 mm Hg. Each curve was S-shaped: it had a lower heart period plateau below threshold pressure, a part where heart period increased monotonically with rising mean arterial blood pressure, and an upper heart period plateau above upper saturation pressure. In spontaneously breathing rabbits, the pressure-dependent parameters of the curves were altered during hypoxia; in addition, there were baroreflex-independent shifts in heart period plateau levels. Suprapontine centers participated in both of these changes. An afferent analysis performed in rabbits treated with atropine and subjected to controlled ventilation showed that the changes in curve parameters were due to afferent interactions in cardiac sympathetic motoneurons between (1) arterial baroreceptor and chemoreceptor inputs which increased threshold, (2) arterial baroreceptor and cardiopulmonary baroreceptor inputs which lowered threshold and increased gain, and (3) cardiopulmonary baroreceptor and chemoreceptor inputs which increased gain and heart period range. Baroreflex-independent shifts in plateau levels were due to increased chemoreceptor and lung inflation receptor activity. The baroreflex-dependent and the baroreflex-independent components of the heart period response were mediated (as in spontaneously breathing rabbits) through both suprapontine centers and pontine centers.

Central Nervous Integration of the Circulatory and Respiratory Responses to Arterial Hypoxemia in the Rabbit

Neural integration during arterial hypoxia was studied in sham-operated, rhinencephalic, thalamic, high mesencephalic, and pontine rabbits, 3 hours after operation under halothane anesthesia. All preparations except the pontine recovered normal movement and posture 40 to 60 minutes after the operation, and effects on the resting circulation specifically ascribable to transection were small. Activation of diencephalic, and to a lesser extent of rhinencephalic, centers was necessary to produce the large increase in autonomic peripheral resistance effect and the autonomic slowing of heart rate characteristic of normal rabbits. In animals with only pontine and high mesencephalic centers, the autonomic peripheral resistance effect was smaller and there was an autonomic rise in heart rate. The neocortex and rhinencephalon exerted inhibitory influences related to the effects of hyperventilation. Suprabulbar respiratory mechanisms were also activated during hypoxia, with diencephalic mechanisms limiting the reflex response mediated by the pontine centers and the cortex exerting disinhibitory effects on the diencephalic centers. The cardiorespiratory response at different degrees of hypoxia probably depends on differences in relative magnitude of inputs from the arterial chemoreceptors, baroreceptors, and lung inflation receptors, producing different degrees of excitation and inhibition of the various suprabulbar and bulbar centers.