Sympathetic Vasoconstrictor Responses Research Articles

Head-up suspension in humans: effects on sympathetic vasomotor activity and cardiovascular responses.

We hypothesized that muscle sympathetic nerve activity (MSNA) and cardiovascular responses to the conventional head-up tilt (HUT) are different from those to head-up suspension (HUS) because of antigravity muscle activity. The MSNA from the tibial nerve, heart rate, blood pressure, stroke volume, cardiac output, and calf blood flow were measured in 13 healthy young subjects. Left atrial diameter was measured by two-dimensional echocardiography in another nine subjects. The resting MSNA and cardiovascular responses at a low level (20 degrees) of orthostasis were similar during both modes. At higher levels (40 and 60 degrees), the responses of MSNA, heart rate, stroke volume, and cardiac output were significantly stronger and there was a smaller reduction in calf blood flow during HUT than during HUS (P < 0.05). Left atrial diameter was decreased significantly from the resting values during HUT and HUS without any significant difference between the modes of orthostasis. The results provide evidence that the engagement of antigravity muscles during HUT may have additive effects on sympathetic vasoconstrictor and cardiovascular responses to orthostatic stress.

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: PHYSIOLOGICAL ACTIONS OF ANGIOTENSIN II MEDIATED BY AT1 AND AT2 RECEPTORS IN THE BRAIN

1. Autoradiographic binding studies have shown that the AT(1) receptor is the predominant angiotensin II (AngII) receptor subtype in the central nervous system (CNS). Major sites of AT(1) receptors are the lamina terminalis, hypothalamic paraventricular nucleus, the lateral parabrachial nucleus, rostral and caudal ventrolateral medulla, nucleus of the solitary tract and the intermediolateral cell column of the thoraco-lumbar spinal cord. 2. While there are differences between species, AT(2) receptors are found mainly in the cerebellum, inferior olive and locus coeruleus of the rat. 3. Circulating AngII acts on AT(1) receptors in the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) to stimulate neurons that may have a role in initiating water drinking. 4. Centrally administered AngII may act on AT(1) receptors in the median preoptic nucleus and elsewhere to induce drinking, sodium appetite, a sympathetic vasoconstrictor response and vasopressin secretion. 5. Recent evidence shows that centrally administered AT(1) antagonists inhibit dipsogenic, natriuretic, pressor and vasopressin secretory responses to intracerebroventricular infusion of hypertonic saline. This suggests that an angiotensinergic neural pathway has a role in osmoregulatory responses. 6. Central angiotensinergic pathways which include neural inputs to the rostral ventrolateral medulla may use AT(1) receptors and play a role in the function of sympathetic pathways maintaining arterial pressure.

A Standardized Bedside Test for Assessment of Peripheral Sympathetic Nervous Function Using Laser Doppler Flowmetry

In spite of increasing knowledge about the role of the sympathetic nervous system in autonomic disturbances like reflex sympathetic dystrophy, no functional test for the peripheral sympathetic system has been introduced into the clinical routine so far. In the development of a standardized bedside test, effects of arousal stimuli [inspiratory gasp (IG) and contralateral cooling (CC)] on blood flow in the fingertips (FTBF) were studied, using laser Doppler flowmetry (LDF). Fifty-two healthy subjects (ages 17 to 75) and 15 patients with sympathetic reflex dystrophy (SRD) underwent the diagnostic procedure. FTBF of healthy subjects during arousal maneuvers showed a reproducible decrease, which is related to a sympathetic vasoconstrictor response. The standardized test procedure with external body heating made interindividual test results comparable. Examination trials with 4 healthy subjects on 10 subsequent days showed good reproducibility. Mathematical analysis of the LDF curves was performed to calculate the degree of FTBF decrease (SRF = (Fmean− Fmin)/Fmean, QI = ∫pre/∫post). In contrast to absolute flow values likeFmeanandFminor time-related parameters liketdecreaseandtregeneration, SRF and QI values presented small coefficients of variation (IG test, SRF 25.7, QI 21.7; CC test, SRF 20.0, QI 15.3). The typical decrease of the LDF signal after sympathetic stimulation was absent or diminished in patients with SRD. SRF and QI values showed statistically highly significant differences (P< 0.001) compared to healthy subjects. The presented test appears reliable for the assessment of peripheral sympathetic nervous function. The narrow physiological range of SRF and QI values enabled the differentiation of pathological sympathetic reactions. The test procedure is easy to perform, noninvasive, and practical even in patients with injuries of the upper limbs.

Functional reinnervation of the vasculature of the adult cat paw pad by axons originally innervating vessels in hairy skin.

Sympathetic vasoconstrictor neurons that had previously innervated blood vessels in hairy skin were made to reinnervate the vasculature of the hairless skin of the paw pad by suturing the central stump of the cut sural nerve to the distal stump of the cut tibial nerve. After allowing sufficient time for the reinnervation, electrical stimulation of the vasoconstrictor pathway in the lumbar sympathetic trunk produced a reduction of the blood flow that was significantly greater than in control animals. There was also a clear sign of a "denervation supersensitivity" of the blood vessels as evidenced by a significantly increased vasoconstriction that followed the systemic application of the alpha 1-adrenoceptor specific agonist phenylephrine. Neurogenic vasodilation evoked by antidromic excitation of small diameter primary afferent neurones was significantly impaired although myelinated and unmyelinated primary afferents had re-grown into the target tissue. Electrical stimulation of the intact tibial nerve (containing sympathetic vasoconstrictor axons and nociceptive primary afferent fibres) in control animals, always produced vasodilatation indicating that the neurogenic vasodilatation can override the sympathetic vasoconstrictor response. By contrast, electrical stimulation of cross-unioned nerves consistently produced a robust vasoconstriction. We conclude that sympathetic vasoconstrictor neurons have a high capacity to functionally reinnervate autonomic effector organs in the adult cat. Despite this functional recovery, the blood vessels exhibited stronger than normal responses to an alpha 1-adrenoceptor agonist. The impaired neurogenic vasodilatation mediated by small diameter afferents may be due to their poor ability to re-establish their efferent vasodilatory function. Alternatively it may be masked by the strong vasoconstriction.

Comparison of synovial PO2 and sympathetic vasoconstrictor responses in normal and acutely inflamed rabbit knee joints

Experiments were performed to assess the effect of acute inflammation of the rabbit knee joint on the partial pressure of oxygen in synovial fluid (Ps,O2) and nerve-mediated vasoconstrictor responses of articular blood vessels. With the hypodermic needle oxygen electrode sited within the synovial cavity in the posterior region of the knee joint, mean (+/- S.E.M.). Ps,O2 was 37.4 +/- 3.6 mmHg (n = 10) in the inflamed group, which differed significantly (P < 0.05) from that occurring in the normal group from a different series (48.2 +/- 3.1 mmHg; n = 18). Ps,O2 was found to decrease with increasing depth of penetration of the oxygen electrode into the joint cavity of the inflamed knee, as in the normal knee. The lowest values were observed close to articular cartilage. Absolute blood flow was measured using radiolabelled microspheres whilst relative changes in blood flow were assessed using laser Doppler flowmetry. The former technique showed that the inflamed joints had a significantly higher blood flow. Electrical stimulation of the posterior articular nerve (PAN) of the knee resulted in vasoconstriction of knee joint blood vessels, which was accompanied by a reduction in Ps,O2. The frequency-response and voltage-response profiles to electrical stimulation of the PAN, although differing in magnitude, showed a high degree of correlation between blood flow and Ps,O2. The frequency-response profile to electrical stimulation of the PAN shifted to the right in inflamed joints compared with normal joints, suggesting a reduction in the efficacy of the sympathetic nervous system in regulating blood flow to the inflamed joints. Although the inflamed joint had a higher blood flow, Ps,O2 was lower compared with the normal joint. The results of this study show significantly altered blood flow, Ps,O2 and nerve-mediated constrictor responses in the acutely inflamed joint. These are related to the inflammatory response and may contribute to the pathogenesis of arthritis.

Effect of baseline vascular tone on vasomotor responses in cat lip.

1. Parasympathetic vasodilator and sympathetic vasoconstrictor responses were monitored using laser Doppler measurement of red cell flux in the lips of anaesthetized and artificially ventilated cats. 2. Three relationships were investigated: (i) that between the reflex parasympathetic vasodilator response induced by lingual nerve (LN) stimulation and baseline red cell flux (BRCF) levels adjusted by repetitive stimulation of the cervical sympathetic nerve (CSN) at various frequencies; (ii) that between the sympathetic vasoconstrictor response elicited by CSN stimulation and the adjusted BRCF levels; and (iii) that between the vasomotor response evoked by simultaneous stimulation of the LN and CSN and the adjusted BRCF levels. 3. The amplitude of the parasympathetic vasodilator response increased as BRCF decreased. In contrast, the amplitude of the sympathetic vasoconstrictor response increased in line with BRCF. 4. Simultaneous activation of the parasympathetic and sympathetic nerves induced a blood flow decrease at high BRCF levels but an increase at low levels. 5. The tendency for the skin of cold subjects to vasodilate and that of warm ones to vasoconstrict in response to various types of stimuli discussed in the light of the present findings.

Capsaicin-induced central facilitation of a sympathetic vasoconstrictor response to painful stimulation in humans

The effect of capsaicin, a compound selectively activating nociceptive primary afferent fibers, on a centrally mediated autonomic (sympathetic) vasoconstriction response to painful peripheral stimulation was studied in healthy human volunteers. Capsaicin (1%) was applied topically to the dorsal forearm and the threshold for eliciting a vasoconstriction response in the contralateral forefinger to painful electrical or thermal stimulation of the forearm skin adjacent to or remote from the capsaicin-treated region was determined with Laser Doppler flowmetry. Capsaicin produced a significant decrease of the threshold for the vasoconstriction response to painful electrical stimulation of the area of central allodynia; i.e., the skin area located adjacent to the capsaicin-treated region in which a light touch evoked an unpleasant sensation. Capsaicin did not change the threshold for the vasoconsriction response to painful heat stimuli applied to the area of central allodynia or to painful electric stimulation applied outside the borders of the allodynic area. Heart rate, blood pressure and heart vagal tone were not modified by capsaicin. It is concluded that a selective activation of nociceptive primary afferent fibers of the skin by capsaicin produces a central submodality-dependent facilitation of an autonomic vasoconstriction response to noxious stimulation in humans. This central facilitation can be explained by segmental excitability changes of afferent interneurons at the spinal cord level.

Effect of baseline vascular tone on vasomotor responses in cat lip

1. Parasympathetic vasodilator and sympathetic vasoconstrictor responses were monitored using laser Doppler measurement of red cell flux in the lips of anaesthetized and artificially ventilated cats. 2. Three relationships were investigated: (i) that between the reflex parasympathetic vasodilator response induced by lingual nerve (LN) stimulation and baseline red cell flux (BRCF) levels adjusted by repetitive stimulation of the cervical sympathetic nerve (CSN) at various frequencies; (ii) that between the sympathetic vasoconstrictor response elicited by CSN stimulation and the adjusted BRCF levels; and (iii) that between the vasomotor response evoked by simultaneous stimulation of the LN and CSN and the adjusted BRCF levels. 3. The amplitude of the parasympathetic vasodilator response increased as BRCF decreased. In contrast, the amplitude of the sympathetic vasoconstrictor response increased in line with BRCF. 4. Simultaneous activation of the parasympathetic and sympathetic nerves induced a blood flow decrease at high BRCF levels but an increase at low levels. 5. The tendency for the skin of cold subjects to vasodilate and that of warm ones to vasoconstrict in response to various types of stimuli discussed in the light of the present findings.

Role of prostaglandins in regulation of blood flow and modulation of sympathetic vasoconstriction in normal and acutely inflamed rabbit knee joints

Experiments were performed to investigate, in the normal and acutely inflamed rabbit knee joint, the role of prostaglandins in the regulation of joint blood flow, measured by laser Doppler flowmetry, as well as their modulation of sympathetic vasoconstriction. Close intra-arterial injection of prostaglandin E2 (PGE2) produced a dose-dependent vasodilatation in control joints, but the responses in inflamed joints were much smaller. Close intra-arterial infusion of indomethacin significantly increased the responses of the control joints to PGE2, but had no effect on the responsiveness of the inflamed joints. Nerve-mediated vasoconstrictor responses did not change significantly with close intra-arterial infusion of indomethacin, either in control or in inflamed joints. Indomethacin infusions decreased basal joint blood flow in the control joint significantly more than in the inflamed joint. The systemic blood pressure was elevated slightly only in the control group. The results of this study show that although prostaglandins have a role to play in regulation of basal blood flow in both normal and acutely inflamed rabbit knee joints, they do not appear to play a significant role in modulation of sympathetic vasoconstrictor responses. Prostaglandin E2 receptors are functional in normal knee joint blood vessels, but they may be disabled by the process of inflammation.

Cardiovascular effects of R- α-methylhistamine, a selective histamine H 3 receptor agonist, in rats: lack of involvement of histamine H 3 receptors

Selective histamine H 3 receptor agonists, such as R- α-methylhistamine, have been shown to inhibit neurogenic sympathetic pressor responses in vivo. The objective of the present study was to test the hypothesis that R- α-methylhistamine would evoke an histamine H 3 receptor mediated hypotensive response in an animal with intact sympathetic vascular tone. In pentobarbital anaesthetized rats, administration of R- α-methylhistamine (0.1–3 mg·kg −1, i.v.) had a biphasic effect on arterial pressure, consisting of a transient depressor response followed by a more long-lasting pressor response. The depressor response was antagonized by chlorpheniramine (selective histamine H 1 receptor antagonist, 3 mg·kg −1, i.v.), but was unaffected by cimetidine (selective histamine H 2 receptor antagonist, 3 mg·kg −1,i.v.) or thioperamide (selective histamine H 3 receptor antagonist, 3 mg·kg −1,i.v). The pressor response was unaltered by chlorpheniramine, cimetidine or thioperamide. In pithed rats, R- α-methylhistamine had a biphasic effect on arterial pressure which was qualitaively similar to that seen in anaesthetized rats with the exception that the pressor responses were much greater in magnitude and duration and were accompanied by significant increases in heart rate. On a pharmacological basis, the biphasic response in pithed rats was identical to that seen in anaesthtized rats inasmuch as the depressor response was antagonized by chlorpheniramine whereas the pressor response was resistant to histamine H 1,, H 2 and H 3 receptor antagonists. Combined α- and β-adrenoceptor blockade (with phentolamine and nadolol) produced significant attenuation of the pressor and tachycardic responses to R- α-methylhistamine in pithed rats. The pressor and tachycardic responses to R- α-methylhistamine were significantly blunted in adrenalectomized rats when compared to sham controls. Chemical sympathectomy, with 6-hydroxydopamine pretreatment, attenuated the tachycardic but not the pressor responses to R- α-methylhistamine. These data suggest that the depressor response to R- α-methylhistamine is mediated via agonism of histamine H 1 receptors, whereas the pressor response, which is mediated in part by adrenal catecholamines, is not due to activation of either histamine H 1, H 2 or H 3 receptors. No evidence was found for the involvement of histamine H 3 receptors in the cardiovascular effects of R- α-methylhistamine.

Cardiopulmonary reflexes do not modulate exercise pressor reflexes during isometric exercise in humans

Previous studies that measured reflex vasoconstrictor responses during isometric exercise have suggested that these responses were modulated by arterial and cardiopulmonary baroreflexes. The purpose of these experiments was to determine forearm vasoconstrictor responses to isometric handgrip alone and during two levels of cardiopulmonary baroreceptor unloading with lower body negative pressure (-5 and -10 mmHg LBNP). Handgrip combined with -5 mmHg LBNP produced vasoconstrictor responses that were significantly greater than the algebraic sum of the separate responses to handgrip and LBNP alone, thus confirming earlier studies. However, with -10 mmHg LBNP, the vasoconstrictor responses to LBNP plus handgrip were not different from the algebraic sum of the separate response to LBNP and handgrip alone. These results indicate that when the influence of cardiac baroreceptors was reduced to a greater degree (-10 mmHg LBNP) than in previous studies, no interaction was observed, whereas with less reduction (-5 mmHg LBNP) an apparent interaction was noted. These data, together with recent studies in which sympathetic nerve activity to the lower leg was measured during similar protocols, suggest nonlinearities in the relationship between sympathetic nerve activity and vasoconstrictor responses.

Acute inflammation in the rat knee joint attenuates sympathetic vasoconstriction but enhances neuropeptide-mediated vasodilatation assessed by laser Doppler perfusion imaging

The effect of sympathetic nerve stimulation and topical application of substance P and calcitonin gene-related peptide on the blood flow of the exposed rat knee joint capsule was investigated. The responses of normal animals were compared to those of animals with acutely inflamed joints induced by intra-articular injection of 2% carrageenan. Laser Doppler perfusion imaging was used to examine the spatial distribution of blood flow in the knee joint capsule. Animals with acute joint inflammation showed markedly reduced vasoconstrictor responses to sympathetic nerve stimulation, but enhanced vasodilator responses to both substance P and calcitonin gene-related peptide when compared to normal. Prior application of either substance P or calcitonin gene-related peptide to the normal joint attenuated sympathetic vasoconstrictor responses. In the acutely inflamed knee, sympathetic vasoconstriction was replaced by a vasodilator response in the presence of neuropeptides. The reduced effectiveness of sympathetically mediated vasoconstriction and enhanced responsiveness to substance P and calcitonin gene-related peptide could contribute to the hyperaemia characteristic of inflamed joints.

Cutaneous vascular responses and thermoregulation in relation to age.

1. Sympathetic vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge were assessed in fingertip skin in relation to age and were correlated with vasoconstrictor ability during body cooling. The above relationship was also examined in diabetic patients in whom vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge had been shown previously to be markedly impaired. 2. Vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge, measured by laser Doppler flowmetry, were significantly reduced in the elderly group, although individual responses varied from normal to absent, and they also had a considerably greater variability as measured on three separate occasions than seen in young subjects. Discriminant analysis showed that, from each of three occasions, 65% of vasoconstrictor responses were abnormal in the elderly group. 3. Body cooling was performed by reducing the environmental temperature from 40 degrees C to 12 degrees C, and the time taken for blood flow to fall to 75%, 50% and 25% of the pre-cooling level (VC75, VC50, VC25, respectively) was calculated. Vasoconstriction was rapid in young subjects and was consistent with good vasoconstrictor responses to inspiratory gasp and contralateral arm cold challenge. In the elderly group, vasoconstriction was slower, but only the VC25 value differed significantly [elderly group, 13.3 (7.9-31.0) min, young group, 5.7 (2.7-15.5) min; median (interquartile range); P less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-ischaemic profile of a new calcium entry blocker: Teludipine

Gillichthys urotensin II (GUII; 1.5–150 nmol kg−1) reduced blood pressure in anesthetized rats, diastolic pressure being reduced to a greater extent than systolic. The effect was slow in onset (peak at 4–5 min) and longlasting (up to 60 min), and was accompanied by a reflex tachycardia. The hypotension was not blocked by propranolol or by mepyramine. In pithed rats, GUII (150 nmol kg−1) reduced the pressor responses to sympathetic nerve stimulation, noradrenaline, and Arg-vasopressin. Somatostatin (150 nmol kg−1) had no effect on the sympathetic pressor response but reduced heart rate. It is concluded that GUII is a vasodilator in the rat, an action not shared with somatostatin.

Local and central sympathetic reflex control of blood flow in skeletal muscle and subcutaneous tissue in normal man

The effect of age and sex on relative changes in blood flow and vascular resistance in skeletal muscle and subcutaneous tissue during postural changes and during local increase in transmural pressure was studied in 33 healthy subjects. The intra-individual variation was studied in five subjects. Blood flow was measured by the local 133Xenon wash-out method. No relation to age or sex was seen in the centrally elicited sympathetic vasoconstrictor responses in subcutaneous tissue and skeletal muscle and in the locally elicited vasoconstriction in subcutaneous tissue. A small, but statistically significant, correlation to sex and age was found in the local sympathetic vasoconstrictor response in skeletal muscle. The age correlation was caused only by an attenuated response in the young subjects below 40 years of age and may be fortuitous. The intra-individual variation was acceptably small. Based on the present results, a reduction in blood flow in skeletal muscle and subcutaneous tissue during centrally or locally elicited sympathetic vasoconstriction of 10% or less should be considered abnormal. The local 133Xenon wash-out method is of value in examining patients suspected of dysfunction in the sympathetic part of the autonomic nervous system.

Different sensitivities of rabbit isolated blood vessels exhibiting co‐transmission to the slow calcium channel blocker, nifedipine

1. Antagonist drugs were used to separate the purinergic and adrenergic contributions as well as the adrenoceptor sub-types involved in the sympathetic vasoconstrictor responses produced by electrical field stimulation in rabbit isolated ileocolic and proximal saphenous arteries. Blocking drugs were applied either alone or in various combinations and sequences. 2. Nifedipine attenuated vasoconstrictor responses to sympathetic nerve stimulation both in the presence and in the absence of alpha-adrenoceptor blocking agents. However in the presence of alpha,beta-methylene ATP, nifedipine produces at best only a small attenuation of the vasoconstrictor response. 3. These results suggest that the purinergic component of the response to sympathetic nerve stimulation, at least in these tissues, can be antagonized by nifedipine, whereas the alpha 1-adrenoceptor-mediated response is relatively resistant.

Interaction of neuropeptide Y and the sympathetic nervous system in vascular control in man.

There is increasing evidence that neuropeptide Y (NPY) contributes to the autonomic control of the circulation. NPY coexists with noradrenaline in perivascular nerve terminals, may be released during sympathetic stimulation, and is a potent constrictor of the human coronary circulation and other vascular beds. In vitro studies show that NPY can act either directly on vascular smooth muscle or indirectly by modulation of the presynaptic release or the postsynaptic actions of noradrenaline. It is unclear to what extent these mechanisms operate in vivo. The effect on forearm blood flow of intra-arterial NPY was studied in six volunteers during coinfusion of noradrenaline and during reflex sympathetic stimulation induced by lower-body negative pressure. NPY alone induced a dose-dependent reduction of forearm blood flow in all subjects studied, to a maximum of 49 +/- 6.1%. The reduction of flow during infusion of noradrenaline alone was 42 +/- 8%. The response to noradrenaline was unaffected by coinfusion of a threshold constrictor dose of NPY (50 pmol/min). Furthermore, the reflex sympathetic vasoconstrictor response to 20 cm H2O of lower-body negative pressure was similar in both the infused and control arms during the infusion of 50 pmol/min NPY. The response to noradrenaline was abolished by alpha-blockade with phentolamine, but the flow reduction induced by NPY was unaffected by alpha-blockade. NPY is a potent constrictor of human forearm resistance vessels and has a direct effect independent of alpha-receptors. NPY has no detectable modulating effect in vivo on the action of endogenous or infused noradrenaline.

A comparison of peripheral vasoconstrictor responses and cardiovascular autonomic function tests in diabetic patients

Venous occlusion plethysmography has been used to measure sympathetic vasoconstrictor responses in the feet and hands to a deep breath and body cooling and to assess blood flow variability. Measurements were made in 14 non-diabetic control subjects and 52 diabetic patients, 30 of whom had evidence of peripheral neuropathy. All the measurements were significantly reduced in the feet of patients with neuropathy. Vasoconstrictor responses were not significantly impaired in the hands of these patients. Cardiovascular autonomic function was assessed in the same subjects by standard tests of reflex heart rate responses and compared to sympathetic vasoconstrictor function as determined by the response to a deep breath. Eighteen of the 30 diabetic patients with peripheral neuropathy had impairment of both cardiovascular and sympathetic vasoconstrictor function. Five had normal vasoconstrictor but impaired cardiovascular responses and two had normal cardiovascular but impaired vasoconstrictor function. It may therefore be important to assess both systems in diabetic patients.

Enhanced Sympathetic Pressor Responses to Intracerebrovascularly Infused Saline in Awake Salt-loaded Rats

Osmotic minipumps were used to infuse hypertonic saline intracerebroventricularly into conscious rats fed high-salt diets to determine if combining high-salt intake with ICV saline infusion would elevate blood pressure more than either procedure alone. Mean aortic pressures became progressively elevated in all rats infused with saline and the magnitude of the elevation was significantly larger in those fed high-salt diets instead of the regular chow. Added pressor effects of high-salt feeding were unaffected by pharmacologic vasopressin or angiotensin blockade thereby indicating that humoral mediation by either peptide was not involved. A general increase in cardiovascular reactivity also seemed unlikely since pressor responsiveness to injected norepinephrine did not differ between rat groups. Sympathetic hyperactivity was considered to be a logical explanation because enhancement by high-salt feeding was abolished following either ganglion blockade with pentolinium or chemical sympathectomy with 6-hydroxydopamine. These findings are compatible with the interpretation that high-salt feeding enhanced pressor responses to centrally-infused saline by increasing sympathetic vasomotor tone.

New insights into pacemaker syndrome gained from hemodynamic, humoral and vascular responses during ventriculo-atrial pacing

Ventricular pacing is performed during programmed electrical stimulation and during normal functioning of single chamber (VVI or VVIR) pacemakers. In many patients, retrograde ventriculo-atrial (V-A) conduction may occur and evoke hemodynamic and reflex neurohumoral responses, which are unique to this pacing mode. Accordingly, forearm blood flow, forearm vascular resistance, mean and phasic arterial pressure, cardiac output and plasma norepinephrine, epinephrine and dopamine were measured during atrial, ventricular and V-A pacing at a cycle length of 600 ms (100 beats/min) before and after regional a blockade with intraarterial phentolamine in 16 patients with a left ventricular ejection fraction >35% and little or no symptoms of congestive heart failure. During V-A pacing, cardiac output decreased by 10%, whereas forearm vascular resistance increased from 52 ± 7 to 70 ± 9 U (p < 0.001) and plasma norepinephrine increased from 183 ± 27 to 232 ± 27 pg/ml (p < 0.01). Phentolamine nearly abolished the increase in forearm vascular resistance in response to V-A pacing (18 ± 4.1 U before vs 5.8 ± 1.5 U after, p < 0.05). The change in forearm vascular resistance with V-A pacing correlated with systolic arterial pressure, but not with changes in mean arterial pressure, pulse pressure, cardiac output, mean or peak right atrial pressure, pulmonary artery or pulmonary capillary wedge pressure. These results suggest that forearm vascular resistance responses to V-A pacing are mediated mainly by α-adrenergic receptors, through the arterial baroreflexes. These sympathetic vasoconstrictor and humoral responses may be important in compensating for hemodynamk abnormalities during ventricular arrhythmias, and inadequate sympathetic responses may play a role in the genesis of pacemaker syndrome.