Sympathetic Vasoconstrictor Responses Research Articles

Unclipping of two-kidney, one clip hypertensive rats produces endothelium-dependent inhibition of sympathetic vasoconstriction.

Removal of the renal artery-constricting clip in two-kidney, one clip (2-K,1C) Goldblatt-hypertensive rats produces a rapid fall in blood pressure which has been attributed to the release of vasodepressor lipids from the renal medulla. The aim of this study was to demonstrate the effect of unclipping 2-K,1C hypertensive rats, and of any hormone thereby released, on vasoconstrictor responses to sympathetic stimulation in the ex vivo blood-perfused tail artery, as well as the role of the vascular endothelium in mediating this effect. Blood was withdrawn at a rate of 2 ml/min from the carotid artery of an anaesthetized 2-K,1C rat and used to perfuse, via an extracorporeal circuit, a cannulated segment of tail artery which had been taken from a killed, normal rat and mounted in an organ bath. The blood was returned to the 2-K,1C rat via the jugular vein. Vasoconstriction and increases in perfusion pressure were produced by periarterial electrical stimulation of the tail artery. The tail artery was either intact or had had its endothelium removed. Sham operations which did not remove the renal artery clip did not change blood pressure or vasoconstrictor responses. Unclipping lowered blood pressure and reduced vasoconstrictor responses in ex vivo blood-perfused tail arteries in which the endothelium was intact, but did not decrease responses in tail arteries from which the endothelium had been removed. It is concluded that unclipping releases a hormone which lowers blood pressure and inhibits sympathetic vasoconstrictor responses via an endothelium-dependent mechanism.

A comparison of vasodilator activity of agents activating cyclic nucleotides with those inhibiting their metabolism in rabbit isolated ear artery

1. The effects of forskolin, a direct activator of adenylate cyclase and sodium nitroprusside, a direct activator of guanylate cyclase, were studied on rabbit isolated ear arteries preconstricted with 80 mM potassium. 2. Bolus injection of these two compounds resulted in vasodilatation. They had similar potencies in this tissue but forskolin had a significantly longer duration of action than sodium nitroprusside. 3. In the same tissue, perfusion with isobutylmethylxanthine (IBMX), a non-selective phosphodiesterase (PDE) inhibitor, or zaprinast, selective for the PDE primarily responsible for the metabolism of guanosine 3':5'-cyclic monophosphate (cyclic GMP), resulted in vasodilatation. However, SK&F 94120 selective for cyclic AMP-PDE (PDE III), primarily responsible for the metabolism of adenosine 3':5'-cyclic monophosphate (cyclic AMP), resulted in vasodilatation only at very high concentrations. The rank order of potency for the compounds was IBMX greater than zaprinast greater than SK&F 94120. 4. The effects of these three PDE inhibitors were studied on the vasoconstriction produced by perivascular sympathetic nerve stimulation in the absence of raised potassium. IBMX and zaprinast, caused a reduction in the response at 50 Hz stimulation frequency and a shift in the frequency-response curve to the right. SK&F 94120 did not displace the frequency-response curve but did reduce the response at 50 Hz. The same order of potency for the inhibition of the vasoconstrictor responses to perivascular sympathetic nerve stimulation was found as for vasodilatation i.e. IBMX greater than zaprinast greater than SK&F 94120. 5. These results indicate that in the same tissue direct activation of adenylate and guanylate cyclase results in vasodilatation. Non-specific PDE and cyclic GMP-PDE inhibition also resulted in vasodilatation and inhibition of vasoconstrictor responses to sympathetic nerve stimulation. However a selective cyclic AMP-PDE (PDE III) inhibitor did not result in vasodilatation, except at very high concentrations, or inhibit sympathetic vasoconstrictor responses except to reduce the response at 50Hz stimulation. These findings provide further support for the ability of PDE inhibitors to be tissue selective.

Renal alpha 1-adrenergic receptor response coupling in spontaneously hypertensive rats.

Renal sympathetic antidiuretic, antinatriuretic, and vasoconstrictor responses are mediated by alpha 1-adrenergic receptors in the normal rat. Since the renal nerve has been implicated in the pathogenesis of rat genetic hypertension, we investigated renal alpha 1-adrenergic receptor coupling to phosphoinositide turnover in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In cortical slices from adult (13-week-old) SHR and WKY, stimulation with norepinephrine (10(-7)-10(-3) M) caused a concentration-dependent increase in accumulation of [3H]inositol phosphates. However, dose-response curves for SHR characteristically displayed a depression of the maximum response as compared with those for WKY. Baseline accumulation of [3H]inositol phosphates was not different between strains (39.4 +/- 2.2 cpm/mg tissue/hr for WKY and 34.4 +/- 2.1 cpm/mg tissue/hr for SHR slices; n = 5 rats/group, determined in triplicate). Antagonist competition studies revealed that norepinephrine-stimulated (10(-4) M) [3H]inositol phosphate accumulation was mediated by alpha 1-adrenergic receptors (IC50) for prazosin: 65 +/- 11 nM for SHR and 64 +/- 5 nM for WKY). The reduction in norepinephrine-stimulated [3H]inositol phosphate accumulation in SHR cortex was not the result of the hypertension, since it was also present in cortical slices from young (4-week-old) SHR in which the blood pressure was not yet significantly different from that in WKY and since [3H]inositol phosphate accumulation was unchanged from control values in rats made hypertensive by treatment with deoxycorticosterone acetate. Scatchard analysis of [3H]prazosin binding in renal cortical membranes of young and adult SHR and WKY revealed no significant differences in alpha 1-adrenergic receptor density or affinity between strains at either age. Our results suggest that renal alpha 1-adrenergic receptor coupling to phospholipase C is less efficient in SHR than in WKY. This impaired response is not the result of hypertension or changes in receptor density; this defect may play a role in increased renal sympathetic nerve activity and in the development or maintenance of hypertension in SHR.

Effect of locally generated angiotensin II on noradrenergic neuroeffector function in the rat isolated caudal artery.

The effects of angiotensin II and its precursors angiotensin I and tetradecapeptide renin substrate were investigated in isolated segments of the rat caudal artery. Each peptide constricted the rat caudal artery and also enhanced vasoconstrictor responses to sympathetic nerve stimulation (0.5 Hz, 10 s). The threshold concentrations for each peptide in enhancing sympathetic vasoconstrictor responses were lower than those required to produce vasoconstriction. Tetradecapeptide renin substrate was the least potent of the three peptides and had the slowest onset of action. Angiotensin II and angiotensin I each enhanced noradrenergic transmission to the same degree, whether perfused through the lumen or added to the adventitial surface of the artery. In contrast, tetradecapeptide renin substrate was more potent when applied to the adventitial surface. The effects of angiotensin I were blocked by the converting enzyme inhibitor enalaprilat, whereas the effects of tetradecapeptide renin substrate were unaltered by enalaprilat, or by the renin inhibitors pepstatin or a decapeptide renin inhibitor. These findings suggest that tetradecapeptide renin substrate and angiotensin I may be converted to angiotensin II within the rat caudal artery, with subsequent enhancement of noradrenergic neuroeffector function. However, the enzyme responsible for the conversion of tetradecapeptide renin substrate cannot be determined from the present findings.

Adrenomedullary and β-adrenergic participation in enhanced sympathetic pressor responses of spontaneously hypertensive rats

The β-adrenergic and adrenomedullary components of pressor to sympathetic nerve stimulation were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The effects of electrical stimulation of the entire spinal cord of pithed rats pretreated with tubocurarine and atropine were studied on systolic bloob pressure, heart rate and plasma cyclic AMP levels. The heart rate increase upon low frequency stimulation (1 Hz) and blood pressure elevation upon stimulation at higher frequencies (3 and 5 Hz) were higher in SHR than in WKY whereas the increase in circulating cyclic AMP level was not different in the two strains. Pretreatment with propranol (2.5 mg·kg −1) further enhanced the pressor responses in SHR but not in WKY, although it inhibited the heart rate acceleration and decreased the circulating level of cyclic AMP similarly in the two strains. After acute adrenalectomy, the elevations of blood pressure and circulating cyclic AMP levels were reduced to an identical level in SHR and WKY. These results show that the marked enhancement of the pressor response observed in SHR upon stimulation of the entire sympathetic outflow is most of adrenomedullary origin and includes a hypotensive component due to β-adrenoceptor stimulation which is not present in WKY.

Inhibitory effect of frusemide on sympathetic vasoconstrictor responses: dependence on a renal hormone and the vascular endothelium.

1. Mesenteric perfusion pressure was measured in the in situ mesentery perfused at a constant rate with blood drawn from the carotid artery of the same anaesthetized rat. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation. These responses were measured before and 30 min after the administration of frusemide (5 mg/kg i.v.) to the rat. Loss of volume due to the frusemide-induced diuresis was prevented by a urinary bladder-venous extracorporeal circuit. 2. Responses to stimulation were reduced after frusemide and were not increased by the subsequent administration of indomethacin (2 mg/kg i.v.). This indomethacin treatment rapidly and completely prevented the fall in blood pressure produced by i.v. arachidonic acid. 3. In rats where the renal papilla had been ablated by treatment with bromoethylamine (200 mg/kg i.p.) 5 weeks previously, frusemide administration did not reduce sympathetic responses in the in situ blood-perfused mesentery. 4. A segment of rat tail artery, cannulated at both ends was mounted in an organ bath and perfused with blood withdrawn from, and returned to, an anaesthetized rat. Increases in perfusion pressure produced by periarterial electrical stimulation of this ex vivo blood perfused tail artery segment were reduced by frusemide administration to the anaesthetized rat. 5. When the endothelium was removed from the tail artery segment, frusemide administration did not lead to any reduction of vasoconstrictor responses. 6. Frusemide may lead to the release of a non-prostanoid hormone from the renal medulla which results in inhibition of peripheral sympathetic vasoconstrictor responses. The release of the hormone may involve intra-renal prostaglandins. The final antivasoconstrictor effect requires an intact vascular endothelium.

Effect of Neuronal Uptake Blockade on the Amplifying Effect of Serotonin on Sympathetic Vasoconstriction in Rat Autoperfused Hindlimb

The effects of serotonin on resting perfusion pressure and on vasoconstrictor responses to electrical stimulation of the lumbar sympathetic outflow were investigated in the autoperfused hindlimb of the pithed rat. beta-Adrenoceptors, muscarinic cholinoceptors, and angiotensin converting enzyme were blocked. Infusion of serotonin (100 ng/min i.a. for 10 min) produced variable increases in hindlimb perfusion pressure of up to 100 mm Hg. During infusion of serotonin, responses to spinal stimulation at 3 Hz for 20 s were decreased, whereas responses at 10 Hz for 10 s were unaffected. Within 5 min of termination of infusion, the direct vasoconstrictor effect of serotonin disappeared, whereas responses to stimulation at both 3 and 10 Hz increased significantly to around 160% of control preinfusion values. In the presence of desipramine (0.1 mg/kg, i.v.), responses to stimulation at 3 Hz were increased; during serotonin infusion the responses were unchanged (i.e., the inhibitory effect observed in the absence of desipramine did not occur), whereas after termination of infusion the responses were again significantly increased. It is concluded that in the rat autoperfused hindlimb, serotonin produces both inhibitory and facilitatory, or amplifying, effects on sympathetic vasoconstrictor responses; increasing the stimulation frequency and neuronal uptake blockade appear to favor the amplifying effect of serotonin.

Inhibition of sympathetic constriction of the ex vivo tail artery perfused with blood from rats given frusemide.

Blood was withdrawn at a constant rate from the cannulated carotid artery of an anaesthetized rat and perfused an ex vivo segment of tail artery cannulated at both ends and contained in an organ bath. Blood returned to the rat via a cannulated jugular vein. The tail artery was constricted and perfusion pressure increased by peri-arterial stimulation at 5 Hz for 5 s every 2 min. Intravenous frusemide (5 mg/kg) decreased the stimulation responses of the tail artery. Diuresis-induced volume losses after frusemide were circumvented by a urinary bladder-intravenous shunt. Frusemide-induced reduction of tail artery vasoconstrictor responses was not seen in nephrectomized rats nor in rats pretreated with indomethacin or saralasin. Indomethacin did not change responses already reduced by frusemide. Exogenous arachidonate or angiotensin II infused into the blood perfusing the tail artery did not alter stimulation responses. We conclude that intravenous frusemide administration to a rat reduces sympathetic vasoconstrictor responses of the ex vivo blood perfused tail artery segment by a diuresis-independent but prostaglandin and angiotensin II dependent release of another hormone from the kidney.

Sodium and vasopressin modulation of renal sympathetic nerve activity.

A series of correlative studies show that sympathetic renal nerve activity (RNA) may be influenced by the concentration of sodium (Na+) in the plasma and the cerebrospinal fluid (CSF). Further study of the sites and characteristics of the interaction between Na+ and the renal nerves was undertaken in anesthetized dogs. Cerebroventricular (i.c.v.) injections of hypertonic sodium chloride (NaCl) produced a sympathetic vasoconstrictor response associated with tachycardia, increases in plasma norepinephrine and vasopressin (AVP), and a decrease in the electroneurographic activity recorded from post-ganglionic renal sympathetic nerves. Both bilateral vagotomy and intravenous administration of an AVP antagonist prevented the decrease in RNA caused by i.c.v. hypertonic NaCl, without markedly reducing the magnitude of the pressor response. The same phenomenon, however, could not be duplicated by delivery of the AVP antagonist i.c.v. In another group of dogs, the pressor activity of NaCl injected into the cisterna magna was compared before and after surgical ablation of the area postrema in the dorsal medulla. Removal of this circumventricular organ attenuated the pressor effects of NaCl given into the cisterna magna, but not those produced by i.c.v. delivery of the injectate. The data suggest that acute increases in CSF Na+ cause a differential activation of the sympathetic nervous system mediated in part by structures at or near the area postrema. At this site, circulating AVP apparently augments the inhibitory input from vagal afferents on the preganglionic renal nerve neurons.

Cardiovascular effects of urotensin II in anesthetized and pithed rats

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.

Presynaptic Dopamine Receptors in the Pithed Rat: Characterization with Apomorphine and Comparison with Central Dopamine Autoreceptors

Apomorphine, a dopamine agonist with high affinity for presynaptic dopamine receptors, caused dose-dependent inhibition (10-300 micrograms/kg intravenously) of the stimulation-induced increase in diastolic blood pressure in the pithed rat. This effect of apomorphine could be antagonized with (-)-sulpiride or haloperidol but not with yohimbine or atropine, indicating the involvement of inhibitory dopamine receptors. The alpha-1-adrenoceptor mediated pressor response to phenylephrine (5 micrograms/kg intravenously) was not significantly attenuated by apomorphine. The sensitivity of peripheral presynaptic dopamine receptors was then studied in the cardiovascular system of rats treated subchronically with haloperidol (2 mg/kg, twice daily intraperitoneally for 10 days). The inhibition of sympathetic vasoconstrictor responses exerted by apomorphine was found to be enhanced after subchronic haloperidol treatment suggesting the development of presynaptic dopamine receptor supersensitivity in the periphery. In addition, the previously reported supersensitivity of central dopamine autoreceptors to low doses of apomorphine could be confirmed in behavioural experiments.

Stress levels of adrenaline amplify the blood pressure response to sympathetic stimulation.

The possibility that sympathetic pressor responses are modulated by adrenaline-mediated facilitation of neuronal noradrenaline release was explored in 17 subjects with borderline hypertension. Infusion of adrenaline, which raised plasma adrenaline by a factor of 8 to 9, augmented the rise in systolic and diastolic arterial pressure induced by standardized cold pressor and isometric exercise tests. The heart rate response to these tests was not affected. When a low dose of propranolol was given on top of the adrenaline infusion before the cold pressor test, the blood pressure response to cold exposure was not different from the response observed when the test was performed during saline infusion. Plasma noradrenaline was higher during adrenaline infusion then during saline infusion, both before and after the cold pressor and isometric exercise tests, and the effect of adrenaline on plasma noradrenaline was antagonized by propranolol. These observations are consistent with the hypothesis that stress levels of circulating adrenaline may amplify sympathetic pressor responses by facilitation of the release of transmitter noradrenaline.

Does dopamine suppress stress-induced intestinal and renal vasoconstriction?

Dopamine interference with intestinal and renal sympathetic reflex vasoconstrictor responses was studied in cats anaesthetized with diazepam, fentanyl and nitrous oxide. Vasoconstriction was induced by electric stimulation of the hypothalamic defence-alarm area and by stimulation of somatic and visceral afferents. In addition, intestinal vasoconstriction was elicited by direct stimulation of postganglionic sympathetic efferent nerves. In the intestine, dopamine administration (7.5 microgram X kg-1 X min-1) was not associated with an attenuation of the investigated sympathetic vasoconstrictor responses, although dopamine per se decreased intestinal vascular resistance by 36 +/- 4%. Due to this dopamine-induced background vasodilation, the intestinal blood flow level during stimulation procedures and concomitant dopamine infusion was higher than during similar stimulations prior to dopamine (for defence-alarm area stimulation 45 +/- 16%, for afferent nerve stimulation 79 +/- 22% and for efferent postganglionic nerve stimulation 66 +/- 16%). In the kidney, dopamine per se had only minor effects on vascular resistance and on changes in vascular tone elicited by the stimulation procedures. The renal blood flow level in response to the stimulation procedures was not significantly affected by dopamine. In conclusion, dopamine may contribute to a sustained intestinal blood flow level when administered during supervening stress-related sympathetic activation.

Sympathetic and local vasoconstrictor response to cold in vibration induced white finger.

To study the relative roles of sympathetic and local vasoconstrictor response to cold in vibration induced white finger (VWF) seven lumberjacks with bilateral VWF and seven age matched controls were investigated. During body cooling finger systolic blood pressure was measured with a cuff technique simultaneously on one affected finger on each hand at 30 degrees, 15 degrees, and 6 degrees C. Both affected fingers had an increased vasoconstrictor response at 15 degrees and 6 degrees C compared with the control group (p less than or equal to 0.05). During unilateral sympathetic nerve block the cold provocation test was repeated on both fingers. The unblocked finger affected by VWF showed no significant difference in the cold response between the two cold provocation tests (p greater than 0.10). The local cold response of blocked finger did not differ from that of the control group (p greater than 0.10). The sympathetic vasoconstrictor response to cold was estimated as the difference between the cold response before nerve block and the cold response during nerve block. The median sympathetic vasoconstrictor response at 6 degrees C was about twice as large as the local response during nerve block (p less than 0.05). The results indicate that the sympathetic vasoconstrictor response to cold plays the dominant part in VWF.

Serotonin enhances sympathetic vasoconstrictor responses in rat isolated perfused tail artery by activation of postjunctional serotonin-2 receptors.

The effects of serotonin and the selective serotonin-2 receptor antagonist ketanserin have been investigated on sympathetic vasoconstrictor responses in rat isolated perfused/superfused proximal tail artery segments. Serotonin (6 nmol/l) markedly enhanced responses to low frequency, short duration electrical stimulation (0.1 ms pulses at 1 Hz for 10 s). Serotonin (6 nmol/l) had a very slight (less than 10 mmHg) direct vasoconstrictor effect. Both the enhancing effect of serotonin on responses to electrical stimulation and the slight direct vasoconstrictor effect were blocked by ketanserin (3 nmol/l). Ketanserin (3 nmol/l) had no significant effect on resting tone or on responses to electrical stimulation. It is concluded that serotonin enhances sympathetic vasoconstrictor responses in rat tail artery by activation of postjunctional serotonin-2 receptors. Blockade of this effect by ketanserin is entirely consistent with its antihypertensive effect in vivo.

Sodium depletion induces adrenergic potentiation at prejunctional site.

The objective of this study was to examine the effect of sodium depletion on basal sympathetic adrenergic vascular tone and vasoconstrictor responses to adrenergic nerve stimulation and norepinephrine in pentobarbital-anesthetized dogs. Mean arterial pressure, tibial blood flow, and tibial vascular resistance were not significantly different between sodium-replete and sodium-deplete dogs. However, plasma renin activity (PRA) was 11-fold higher in sodium-deplete dogs (P less than 0.01). Sympathetic denervation in sodium-replete and -deplete dogs resulted in a similar decrease in tibial vascular resistance. Nerve stimulation at 0.25 and 0.5 Hz caused 40 +/- 5 and 48 +/- 5% decreases, respectively, in tibial blood flow in sodium-replete dogs and 71 +/- 3 and 77 +/- 3% decreases, respectively, in sodium-deplete dogs (P less than 0.01). Responses to norepinephrine administered intra-arterially were similar in both groups. Neither captopril nor saralasin reduced the potentiated responses to nerve stimulation in sodium-deplete dogs. Bilateral nephrectomy 24 h prior to the experiment reduced PRA to an undetectable level in both sodium-replete and -deplete dogs and equalized the responses to nerve stimulation and norepinephrine in both groups. Because bilateral nephrectomy, but neither captopril nor saralasin, abolished the potentiated responses in sodium depletion, a renal hormone other than renin or vascular angiotensin II may be responsible for this prejunctional adrenergic potentiation.

Characterisation of smooth muscle alpha-adrenoceptors and of responses to electrical stimulation in the cat isolated perfused middle cerebral artery.

The effects of periarterial electrical stimulation and of drugs with α-adrenoceptor agonist or antagonist activity were examined in cat isolated perfused middle cerebral arteries, in order to characterise the smooth muscle adrenoceptors. The perfused vessel preparation was stable and did not develop intrinsic tone when perfused at 5 ml/min with Krebs' solution. Exogenous noradrenaline caused increases in perfusion pressure, the pD2 value being 6.8±0.1. The maximum effect of noradrenaline was only 22±4% of that of KCl (127 mM). Adrenaline was equipotent with noradrenaline whereas dopamine and phenylephrine were approximately 100 times less potent. The α2-adrenoceptor antagonist RX 781094 (0.1–10 μM) caused concentration-dependent rightward shifts in the noradrenaline concentration-response curve (in the presence of 4μM cocaine and 1 μM propranolol), although the antagonism was not of a simple competitive nature. Prazosin (0.3 μM) failed to produce a significant shift to the right in the concentration effect curve to noradrenaline; however, the effects of maximal concentrations of noradrenaline were slightly but significantly reduced. If tone was induced in the vessels, tetrodotoxinsensitive dilatations could be produced by electrical stimulation. In the absence of tone, the same stimulation parameters were ineffective in causing vasoconstriction. Increasing pulse width or voltage led to substantial vasoconstrictor responses, which were resistant to tetrodotoxin. These results demonstrate that in a cerebral artery which does not show a sympathetic vasoconstrictor response to electrical stimulation, both α1- and α2-adrenoceptors appear to be present on smooth muscle cells although the responses to exogenous noradrenaline are predominantly mediated by the α2-adrenoceptor subtype.

Arrhythmias in the first hours of acute myocardial infarction

R EPORTS of arrhythmias complicating myocardial infarction usually concern those observed in the Coronary Care Unit (CCU). However, the median time between the onset of symptoms and admission to a CCU may be more than 8 hr.’ In an endeavor to document the incidence of arrhythmia in the acute phase of infarction and to obtain information about their etiology, a prospective study was made of 294 patients who were observed and monitored within 1 hr after the onset of chest pain. A high incidence of arrhythmias was observed among the 294 patients (Table 1). Bradyarrhythmia within the first hour occurred in 34% and was most frequent among patients with posterior infarction (Table 2). When atrioventricular block developed in patients with posterior infarction, it was apparent within the first hour. Ventricular ectopic beats occurred in 93% of patients within 4 hr. Ventricular tachycardia and supraventricular tachycardia were comparatively uncommon during the acute phase. The incidence of ventricular fibrillation among 294 patients observed within 1 hr of the onset of infarction was 19%. Among the 55 who developed ventricular fibrillation, 41 (75%) did so within 2 hr and 46 (84%) within 4 hr of the onset of chest pain (Fig. 1). Those who developed ventricular fibrillation often did so without warning ventricular ectopic activity or despite apparently adequate antiarrhythmic therapy. Others workers have also questioned the value of warning ventricular ectopic activity in predicting ventricular fibrillation. Prophylactic antiarrhythmic agents appeared less successful in the acute phase of myocardial infarction than when given later. Assessment of the autonomic nervous system at the onset of infarction was attempted, since it was postulated that a relationship might exist between ventricular arrhythmias and autonomic dysfunction. Assessment was impossible in those patients who presented with ventricular fibrillation, ventricular tachycardia, or supraventricular tachycardia and in those who have been on digitalis or beta-blocking drugs prior to the onset of acute infarction. Patients with a history of hypertension and those with left bundle branch block or combined anterior and posterior infarction were also excluded. Analysis of autonomic status was therefore limited to 240 of the 294 patients and was based on analysis of blood pressure and heart rate data. Patients with sinus tachycardia at the initial examination were considered to have sympathetic overactivity. Transient hypertension (blood pressure 160/l 00 mm Hg or greater) in the absence of sinus tachycardia was also regarded as evidence of sympathetic overactivity, as a sympathetic pressor response with minimal alteration in heart rate has been described.2.3 Patients with sinus bradycardia or atrioventricular block (second degree or complete) were considered to show parasympathetic overactivity. Transient hypotension (systolic blood pressure 100 mm Hg or less) in the absence of bradycardia was also regarded as evidence of parasympathetic overactivity. Eighty-nine of the 240 patients were seen within 30 min. Only 15 (I 7%) of the 89 had a normal heart rate and a normal blood pressure when first seen (Fig. 2). Over one-third showed evidence of sympathetic overactivity. Parasympathetic overactivity was present in almost half the patients. The systolic blood pressure at the initial examination was not greater than 80 mm Hg in nearly one-quarter of the patients. Forty seven percent of the patients with bradyarrhythmia had a systolic blood pressure not greater than 80 mm Hg. Eight percent of all patients seen within 30 min had complete atrioventricular block; none of these had a systolic blood pressure greater than 80 mm Hg. The mean heart rates and blood pressures are shown in Table 3. The incidence of autonomic disturbance was related to the site of infarction (Fig. 3). Para-

Presynaptic inhibition of canine renal adrenergic nerves by acetylcholine in vivo

Experiments were performed in anesthetized dogs to determine whether previously reported in vitro inhibition of sympathetic neurotransmitter release by acetylcholine could be demonstrated in the renal vasculature of the intact animal. Vasoconstrictor responses to renal sympathetic nerve stimulation at varying frequencies were compared to intra-arterial injections of norepinephrine before and during intra-arterial infusions of acetylcholine, 2.5--80 micrograms/min. The vasoconstrictor responses to nerve stimulation were inhibited to a greater extent than were responses to norepinephrine during infusions of acetylcholine. The inhibitory effects of acetylcholine on nerve stimulation were dose and frequency dependent. The inhibition was blocked by atropine but not altered by physostigmine. Changes in renal blood flow per se did not contribute to the inhibitory effect of acetylcholine, since another vasodilator agent, sodium acetate, did not affect the nerve stimulation-norepinephrine vasocontriction relationship. Thus, acetylcholine produced inhibition of in vivo renal sympathetic vasoconstrictor responses, and the receptor involved appears to be muscarinic.

Influence of local insults on sympathetic vasoconstrictor control in feline dental pulp

The present investigation was undertaken to ascertain whether local insults can affect the sympathetic vasoconstrictor regulation of pulpal blood flow. The rate of disapperance (k-value) of iodide from dentinal cavities was measured in anaesthetized cats. Changes in k-value reflected changes in blood flow. It has previously been shown that stimulation of sympathetic vasoconstrictor nerve fibres generally causes a clearcut decrease in the k-value. Deep cavity preparation was found to inhibit the vasoconstrictor response in a few cases in experiments on mature cats. Heating or cooling the tooth during cavity preparation induced a more frequent inhibition, which proved to be reversible within a few hours. Compound 48/80 applied locally to the cavity was also found to induce inhibition of the vasoconstrictor effect, but in this case no sign of reversibility was observed. Chronic insults were produced by exposing the cavity to oral microorganisms during 1-4 weeks before the experimental procedure. In this case, the sympathetic vasoconstrictor response was not inhibited. A histological study was performed to examine the pulp tissue after cavity preparation and the application of insults. It was found that cavity preparation and acute insults caused little or no disturbance, while chronic insults resulted in severe damage to the pulpal tissue.