Α-adrenergic Blockade Research Articles

Antihypertensive Effects of Ketanserin and Ritanserin in the Spontaneously Hypertensive Rat

Acute as well as chronic treatment with ketanserin but not with ritanserin reduced the blood pressure in the spontaneously hypertensive rat, indicating that 5-HT2-receptor blockade alone does not have antihypertensive properties. Whereas the blood pressure reduction to acute administration of ketanserin was directly related to its ability to shift the dose-response curve of phenylephrine (alpha 1-adrenergic blockade), the same relationship was not apparent following chronic treatment with ketanserin. This suggests that the 5-HT2- and alpha 1-blockade may complement each other in reducing the blood pressure, a conclusion supported by the observation that in the conscious rat, 5-HT2-receptor blockade by ritanserin enhanced the hypotensive response to prazosin. However, ritanserin did not influence the ability of prazosin to antagonize pressor responses to phenylephrine in the pithed rat.

Hypothalamic food intake regulating areas are involved in the homeostasis of blood glucose and plasma FFA levels

The hypothalamus fulfills multiple functions, e.g., integration of food and water ingestion, various forms of social behavior and physiological neuroendocrine activities. Hypothalamic areas, particularly the ventromedial, lateral and paraventricular areas (VMH, LHA and PVN respectively), that contribute to the regulation of food intake are also involved in the regulation of blood glucose and plasma free fatty acid (FFA) levels. This regulation is controlled both directly via neural pathways and indirectly by hormones, e.g., insulin, glucagon, norepinephrine (NE) and epinephrine (E). A description is presented of the intrahypothalamic connections and the pathways between the hypothalamus and the motor areas of both the sympathetic system in the spinal cord (the intermediolateral column IML) and the parasympathetic system in the brainstem (the dorsal motornucleus of the vagus and the nucleus ambiguus). Noradrenergic stimulation of the LHA, VMH and PVN can alter blood glucose, plasma FFA and insulin levels independently of each other, e.g., noradrenergic stimulation of the VMH leads to an increase of insulin, glucose and FFA. Exercise induced increases of glucose are suppressed by α-adrenergic blockade of the LHA, VMH and PVN. Alpha-adrenergic blockade of the VMH during exercise causes an exaggerated increase of plasma FFA whereas α-blockade of both the LHA and PVN does not change the normal exercise induced increase of plasma FFA. The apparent contradiction that both adrenergic stimulation and adrenergic blockade of the VMH result in an increase in FFA may be explained by assuming postsynaptic α- and β-adrenergic receptors in the VMH controlling glucose and FFA release respectively and FFA release and presynaptic inhibitory α-adrenergic receptors. Many of these changes are mediated through the circulating catecholamines NE and E. This humoral mechanism may also contribute to the regulation of complex cardiovascular changes that occur in relation to sympathetic activation during energy expenditure such as exercise.

α-Adrenergic Blockade Improves Glucose-Potentiated Insulin Secretion in Non-Insulin-Dependent Diabetes Mellitus

The impairment of glucose-potentiated insulin secretion present in non-insulin-dependent diabetes mellitus (NIDDM) can be approximated in normal subjects by an epinephrine infusion. Therefore, we sought to determine the role of the endogenous sympathetic nervous system in glucose-potentiated insulin secretion in both NIDDM (n = 6) and normal (n = 6) subjects. Glucose-potentiated insulin secretion was calculated as the slope of the curve relating increasing ambient glucose levels to the acute insulin response to an intravenous pulse of 5 g of L-arginine. Glucose-potentiated insulin secretion was determined on separate days during alpha-, beta-, and combined alpha- plus beta-adrenergic blockade and compared with a saline control. In normal subjects, there was no effect of alpha-, beta-, or alpha- plus beta-blockade on the slope of glucose potentiation. In NIDDM, the initially decreased slope of glucose potentiation (0.25 +/- 0.06 microU X ml-1 X mg-1 X dl, mean +/- SE; P less than .01) was not affected by beta-blockade but increased during alpha-blockade (0.91 +/- 0.22 microU X ml-1 X mg-1 X dl; P less than .05). However, this improvement was abolished by combined alpha- plus beta-blockade (0.32 +/- 0.07 microU X ml-1 X mg-1 X dl). Plasma norepinephrine was increased above basal levels in both normal (+260 +/- 89 pg/ml) and NIDDM (+438 +/- 162 pg/ml) subjects during alpha-blockade (P less than .05 for both). This increase in plasma norepinephrine strongly suggests that there is an increase in synaptic cleft norepinephrine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of α-Adrenergic Blockade in the Cardiovascular Actions of Ketanserin

It remains to be established whether ketanserin's antihypertensive effect is caused by S2-serotonergic blockade, by α1-adrenergic blockade, or by a combination of both. Ketanserin, 10 mg i. v. or 40 mg t.i.d. orally, blocked the serotonin-induced contractions of hand veins in patients with essential hypertension. Intravenous ketanserin had no effect on the veno-constrictor action of noradrenaline. The increase in digital blood flow after i.v. ketanserin, as measured by the change in digital skin temperature in patients with Raynaud's phenomenon, was not blocked by phentolamine or pretreatment with prazosin. Intravenous ketanserin also lowered arterial pressure in patients with autonomie insufficiency who were unresponsive to phentolamine. These observations suggest that α-adrenergic blockade is not the sole mechanism of ketanserin's cardiovascular actions in humans.

Role of α-Adrenergic Blockade in the Cardiovascular Actions of Ketanserin

It remains to be established whether ketanserin's antihypertensive effect is caused by S2-serotonergic blockade, by alpha 1-adrenergic blockade, or by a combination of both. Ketanserin, 10 mg i.v. or 40 mg t.i.d. orally, blocked the serotonin-induced contractions of hand veins in patients with essential hypertension. Intravenous ketanserin had no effect on the venoconstrictor action of noradrenaline. The increase in digital blood flow after i.v. ketanserin, as measured by the change in digital skin temperature in patients with Raynaud's phenomenon, was not blocked by phentolamine or pretreatment with prazosin. Intravenous ketanserin also lowered arterial pressure in patients with autonomic insufficiency who were unresponsive to phentolamine. These observations suggest that alpha-adrenergic blockade is not the sole mechanism of ketanserin's cardiovascular actions in humans.

Differences in Vasodilating Action Between Ketanserin, a 5-HT2-Serotonergic Receptor Antagonist, and Terazosin, α1-Adrenoceptor Antagonist, in Anesthetized Rabbits

It has not yet been demonstratcd clearly whether thc antihypertensive action of ketanserin is due to 5-hydroxy-tryptamine type-2 (5-HT2)-serotonergic receptor blockade or to α1-adrenergic rercptor blockade. The present study was performed to evaluatc in vivo the antihypcrtensive action of ketanserin in comparison with that of terazosin, a selective α1-adrenoceptor antagonist. The changes of renal blood flow (RBF) after intrarcnal injection of phenylephrine, 5-HT, or angiotensin II were measured in anesthetized rabbits. RBF responses induced by these vasoconstrictors with or without pretreatment with ketanserin (0.2, 1.0, and 5.0 mg/kg, i.v.) or terazosin (0.04, 0.2, and 1.0 mg/kg, i.v.) were examined. Following intrarcnal injection, RBF decreased by 20.8%, 22.7%, and 23.0% respectively, without ketanserin and also decreased by 21.0%, 21.6%, and 24.4%, respectively, without terazosin. Following pretreatment with a stnall dose of ketanserin or terazosin, the vasoconstricting effects of phenylephrine were attenuated by 20% or 62% (Δ% changes in RBF), respectively. The effects of 5-HT on RBF responsiveness were blocked by ketanserin in a dose-dependent manner. Ketanserin did not modify the RBF responses to angiotensin II. These findings indicate that the antihypertensive effect of ketanserin, to a certain extent, depends on the blockade of the 5-HT2-serotonergic receptor in addition to that of the α1-adrenoceptor, whereas the renin-angiotensin system is not involved in the hypotensive effects of ketanserin.

Do catecholamines contribute to the effects of neonatal hypoxia on development of brain and heart? Influence of concurrent α-adrenergic blockade on ornithine decarboxylase activity

Hypoxia in the neonate releases catecholamines from the adrenal medulla, a response which is necessary to survive. This study examines whether a similar dependence exists for the ability of brain and heart tissue to recover from hypoxia-induced damage, as assessed by measurements of ornithine decarboxylase (ODC) activity. Hypoxia at either 1 day or 8 days of age produced a subsequent elevation of brain ODC which persisted for 1 week, a pattern known to be associated with recovery from tissue damage and delayed cellular maturation. Pretreatment of the rats with phenoxybenzamine, an α-receptor blocking agent, resulted in attenuation of the long-term ODC response, but did not interfere with effects on the enzyme during the hypoxia itself. In the heart, hypoxia at 8 days of age displayed similar effects, with long-term ODC elevations which were attenuated by phenoxybenzamine. Hypoxia at 1 day of age also produced long-term heart ODC stimulation, but in this case the effect was exacerbated by phenoxybenzamine, an effect consistent with the greater dependence of cardiac tissue on α-receptor-mediated responses to hypoxia at that age. These results suggest that α-receptor stimulation by catecholamines released during neonatal hypoxia play a role in the metabolic adjustment of brain and heart tissue to damage and may aid in subsequent recovery.

Protection of the small intestine from nonocclusive mesenteric ischemic injury due to cardiogenic shock

In a pericardial tamponade model of cardiogenic shock in pigs, we had previously shown that acute reductions in cardiac output produce severe mesenteric ischemia due to disproportionate splanchnic vasoconstriction. In this study, we extended the period of cardiogenic shock in order to investigate the pathogenesis of ischemic injury to the small intestinal wall. Four hours of tamponade produced sustained changes in splanchnic hemodynamics, similar to those observed in theprior short-term experiments. The resultant mesenteric ischemia caused necrotic lesions of the small intestine which were characteristic of those seen in nonocclusive mesenteric ischemia in human subjects. Prior αadrenergic blockade failed to prevent either sustained mesenteric vasospasm or ischemic injury. In contrast, prior blockade of the renin-angiotensin axis, whether by nephrectomy or angiotensin-converting enzyme inhibition, blocked the splanchnic vasoconstriction, and thereby protected the small intestine from ischemic injury. The primary hemodynamic and pathologic features of this model of nonocclusive mesenteric ischemia appear to be mediated by the renin-angiotensin axis.

Antihypertensive Mode of Action of Ketanserin

The mechanism of blood pressure reduction by ketanserin in hypertensive patients is still not fully understood. It can occur in the absence of evident alpha 1-adrenergic blockade. However, particularly with prolonged therapy, features of alpha 1 blockade appear. There are both similarities and differences between the pattern of effects caused by ketanserin and prazosin. A central mode of action of ketanserin contributing to the blood pressure reduction is not excluded. It appears unlikely, however, that inhibition of aldosterone secretion makes a substantial contribution to the antihypertensive effect of ketanserin in humans.

Regulation of the right coronary circulation during a controlled behavioral stress in the conscious dog

Right coronary blood flow (CBF) was measured in 11 mongrel dogs during classical aversive conditioning (a 30 s tone followed by a 1 s 2–6 mA electrical shock). The cardiovascular response consisted of significant ( P < 0.01) increases in: (a) mean arterial pressure (12.9%), (b) systolic right ventricular pressure (RVP, 31.8%), (c) d(RVP)/ dt (49.9%) and heart rate (56.2%). The coronary vascular response to behavioral stress consisted of an immediate and significant increase in mean CBF (56.9%) coupled with a significant decrease in mean coronary vascular resistance (CVR, −28.5%). The mean CVR decrease was reduced by cardioselective β-blockade (CBB) or cardiac pacing and eliminated by right stellectomy (RSGx). The combination of CBB with cardiac pacing resulted in a significant increase in mean CVR. α-adrenergic blockade with either phentolamine or prazosin, RSGx, and cardiac pacing significantly reduced the control mean CVR values. Thus, these data suggest that the right coronary response to stress is primarily mediated by the release of metabolic factors secondarily to an increased inotropic or chronotropic state. However, when these metabolic effects were controlled, mean coronary resistance no longer decreased but, rather, increased in response to the aversive stress. This increase could be eliminated by the addition of an α-adrenergic antagonist. These data further suggest that the coronary response to behavioral stress activates an α-adrenergic vasoconstriction.

Relaxations of Isolated Rabbit Coronary Artery by Purine Derivatives

The pharmacological nature of purinoceptors in the rabbit coronary artery was investigated by comparing the extent of vasorelaxation induced by various purine derivatives, with or without amino group at C6 and with or without ribose at N9 in the purine structure. These derivatives were grouped according to structure--adenosine, inosine, adenine, and hypoxanthine analogs. The vasorelaxations produced by adenosine analogs were inhibited by aminophylline, while relaxations produced by the other three groups were unaffected. In the case of adenosine analogs, modification of amino group at C6 to secondary amine resulted in reduction of the potency of the vasorelaxing effect. The order of potency was as follows: adenosine greater than N6-(L)-phenylisopropyladenosine greater than N6-(D)-phenylisopropyladenosine greater than N6-cyclohexyl-adenosine greater than N6-(2,5-dioxo-3-pyrrolidinyl)-adenosine greater than kinetine riboside greater than N6-methyladenosine. On the other hand, the aminophylline-resistant relaxations of adenine analogs were augmented by modification of amino group at C6 to secondary or to tertiary amine. The order of potency was as follows: 6-cyclohexylaminopurine greater than 6-dimethylaminopurine greater than kinetine greater than 6-methylaminopurine adenine. Of adenosine, N6-cyclohexyladenosine, adenine, C6-cyclohexylaminopurine, and inosine, N6-cyclohexylaminopurine was the most potent phosphodiesterase inhibitor of crude enzyme prepared from rabbit aorta. From the order of potency of relaxations produced by adenosine analogs, adenosine receptors in the rabbit coronary artery seem to be of the A2-subtype. The relaxation induced by aminophylline-resistant adenine analogs may be due to activation of an unknown but specific site, since there is a structure-activity relationship in the relaxations produced by this group. Such relaxations may be linked to inhibition of phosphodiesterase in the rabbit coronary artery.

Increased quinidine plasma concentrations during administration of verapamil: A new quinidine-verapamil interaction

A number of drug interactions that involve quinidine have been reported. 1 These include both pharmacokinetic interactions in which plasma concentrations of other drugs, most notably digoxin, are influenced by quinidine, and pharmacologic interactions. The latter is exemplified by a recent report of marked hypotension when intravenous verapamil was given to patients receiving oral quinidine preparations. 2 This hypotension was presumably due to α-adrenergic blockade and the peripheral vasodilatation was a result of both quinidine and verapamil. We report a patient with cyanotic congenital heart disease and atrial flutter with 1:1 atrioventricular conduction who had a previously unreported quinidine-verapamil pharmacokinetic interaction.

Coronary Blood Flow During Exercise Following Nonselective and Selective α1Adrenergic Blockade with Indoramin

Studies were performed to compare the effects of alpha 1-adrenergic blockade with indoramin and nonselective alpha-adrenergic blockade with phentolamine on coronary blood flow and myocardial oxygen consumption during exercise. Nine dogs trained to run on a motor-driven treadmill were instrumented with electromagnetic flowmeter probes on the left circumflex coronary artery, and aortic and coronary sinus catheters for determination of myocardial arteriovenous oxygen difference. During control conditions, myocardial oxygen consumption and coronary blood flow increased as a direct function of heart rate during exercise. Phentolamine caused a significant decrease in blood pressure, while heart rate, coronary blood flow, and myocardial oxygen consumption were significantly increased at rest and during all exercise stages. Although alpha 1-adrenergic blockade with indoramin caused a similar reduction of arterial pressure, heart rate was unaltered both at rest and during exercise. Coronary blood flow and myocardial oxygen consumption were unchanged by alpha 1-adrenergic blockade at rest and during light exercise: however, during the heaviest exercise stages alpha 1-blockade caused a significant decrease in myocardial oxygen consumption. These findings are in agreement with the concept that phentolamine, by blocking presynaptic alpha 2-adrenoceptors which normally modulate norepinephrine release, increases sympathetic activity during exercise while indoramin, by acting as a selective alpha 1-adrenergic blocker, does not produce this effect.

Catecholamine-Mediated Reduction in Uteroplacemental Blood Flow in the Diet-Restricted, Term-Pregnant Rat

To determine whether the reduction in maternal placental blood flow associated with malnutrition during pregnancy results from α-adrenergic vasoconstriction, we measured cardiac output, uteroplacental blood flow and uteroplacental vascular resistance in ad libitum-fed and in 50% diet-restricted term-pregnant rats, using radioactive-labeled microspheres before, and again after, α-adrenergic receptor blockade with phenoxybenzamine. Uteroplacental blood flow in the diet-restricted rats was 40% lower than that of the ad libitum-fed rats, before phenoxybenzamine. Phenoxybenzamine caused a 50% reduction in mean blood pressure in both the ad libitum-fed and diet-restricted rats, but did not alter cardiac output. Phenoxybenzamine decreased preplacental vascular resistance in the diet-restricted rats, resulting in no significant reduction of placental blood flow. In the ad libitum-fed rats, on the other hand, phenoxybenzamine did not alter preplacental vascular resistance, and placental blood flow decreased 45% with the fall in blood pressure. Myometrial vascular resistance was unaffected by phenoxybenzamine in either group, and myometrial blood flow decreased with the fall in blood pressure in both groups. Thus, the decreased uteroplacental blood flow associated with diet restriction is the result of increased uteroplacental α-adrenergic vasomotor tone.

α- and β-adrenergic mechanisms mediate blood pressure control by norepinephrine and angiotensin in ducks

Adrenergic mechanisms for the pressor actions of blood-borne l-norepinephrine (NE) and fowl angiotensin II (ANG II) were studied in barbiturate-anesthetized adult ducks ( Anas platyrhynchos). NE (1.5–6.0 nmol · kg −1) or ANG II (0.4–1.6 nmol · kg −1) injected iv caused dose-dependent increases in mean arterial pressure ( P a) and pulse pressure ( P p) but slowed cardiac frequency ( f H); higher doses of ANG II increased P a, P p, and f H. β-Adrenergic blockade by propranolol lowered baseline P a, completely blocked cardiovascular responses to isoproterenol, augmented the bradycardic effect of NE, and inhibited the stimulation of P p by ANG II. However, the tachycardiac effect of high-dose ANG II persisted during β-blockade. α-Adrenergic blockade following iv prazosin completely blocked the pressor effect of methoxamine, diminished the pressure response to NE, and decreased P a sensitivity to ANG II injections. Combined α- and β-adrenergic blockade decreased both the sensitivity and the maximal P a response to ANG II. We conclude that (i) β-adrenergic mechanisms predominate in the maintenance of resting P a, (ii) NE increases P a principally by α-adrenergic action while β-adrenergic stimulation buffers the consequent bradycardia, and (iii) although the positive chronotropic effect of high doses of ANG II probably is not mediated by catecholamines, low doses of ANG II elevate P a and P p by α- and β-adrenergic mechanisms.

Chapter 20 Morphofunctional studies on the neuropeptide Y/adrenaline costoring terminal systems in the dorsal cardiovascular region of the medulla oblongata. Focus on receptor-receptor interactions in cotransmission

Publisher Summary The morphological studies in the past have been performed by means of computer-assisted morphometry and microdensitometry to give an objective representation of the central adrenaline (A) nerve cell groups in the medulla oblongata. The functional and biochemical studies of the A neurons within the medulla oblongata, especially within the dorsal cardiovascular region, have given evidence that the adrenergic neurons have an important vasodepressor function in the central nervous system (CNS). The existence of neuropeptide Y–like immunoreactivity in the A cell groups C1, C2, and C3 in the medulla oblongata has been demonstrated by studies in the past. Based on these observations, the effects of centrally administered neuropeptide Y (NPY) on cardiovascular and respiratory parameters and on pre- and postsynaptic mechanisms in central A nerve terminal networks in the dorsal cardiovascular region of the medulla oblongata of the rat have been analyzed. These studies have shown that NPY given intracutaneously in the α-chloralose anesthetized rat can reduce arterial blood pressure and heart rate. These actions have been observed in the presence of α-adrenergic receptor blockade.

Adrenergic and dopaminergic control of the canine paw microcirculation

Basal isolated canine paw blood flow was equally distributed between arteriovenous anastomosis (AVA) and capillary circulations. Norepinephrine decreased AVA flow by 92% and capillary flow by 41%. Dopamine significantly reduced AVA flow by 94% compared to baseline with a 37% reduction in capillary flow. However, with α-adrenergic blockade dopamine decreased AVA flow 66% while capillary flow increased 42%. Isoproterenol increased capillary flow almost twofold and appeared to decrease AVA flow, although the latter was statistically insignificant. Differential effects of adrenergic and dopaminergic agonists on canine paw AVA and capillary blood flow suggest the existence of independent regulation of these components of the microcirculation.

Regulation of coronary resistance vessels and large coronary arteries

There is now considerable evidence for α-adrenergic regulation of coronary resistance vessels and large coronary arteries based on studies of chronically instrumented, conscious animals. Infusion of norepinephrine at low doses causes reduction of coronary blood flow with a slight increase in arterial pressure, indicating intense coronary vasoconstriction. This coronary constrictor response was reversed to coronary vasodilation with infusion of norepinephrine after α-adrenergic blockade. Stimulation of α 1- and α 2-adrenergic receptors with phenylephrine and B-HT 920, respectively, also increased calculated coronary vascular resistance in the conscious animal. These effects were eliminated by selective α 1-adrenergic blockade with prazosin and by selective α 2-adrenergic blockade with rauwolscine. Stimulation of the carotid chemoreceptor reflex elicits a period of intense coronary vasoconstriction, characterized by a decrease in coronary blood flow despite increased arterial driving pressure. This response was eliminated by prior α-adrenergic blockade or a combination of cardiac sympathetic denervation and adrenalectomy. Using chronically implanted ultrasonic crystals to measure the epicardial coronary diameter instantaneously and continuously in conscious dogs, marked vasodilation of the large coronary arteries was observed with administration of nitroglycerin or calcium-channel antagonists; in contrast, activation of α-adrenergic receptors with methoxamine induced substantial constriction, characterized by a reduction in coronary artery diameter in the face of elevated distending pressure. The regulation of large coronary arteries is further complicated by the fact that these vessels are responsive to changes in myocardial metabolic demands and coronary blood flow. This was demonstrated by examining responses to brief periods of myocardial ischemia, which induced intense reactive dilation, i.e., dilation of the large coronary artery immediately after the reactive hyperemia response. The dilation of the large coronary artery was not observed after brief periods of myocardial ischemia, when the marked increase in coronary blood flow (reactive hyperemia) was prevented. These findings suggest that coronary artery vasconstriction may be more intense under conditions in which blood flow cannot increase, for example, in the presence of severe stenoses.

Hypertensice response to saline microinjection in the area of the nucleus tractus solitarii of the rat

We investigated the blood pressure response elicited by microinjection of various hypertonic solutions into the area of the nucleus tractus solitarii (NTS) of the brainstem, an area rich in catecholaminergic neurons. Equiosmolar solutions of NaCl, dextrose, LiCl and KCl were employed. NaCl produced a prolonged blood pressure rise; LiCl and normal saline produced a similar rise of short duration; and KCl produced epileptic-type seizures with postictal hypertension. Dextrose had no effect and neither had NaCl microinjection in areas relatively distant from the NTS. The rise in blood pressure was not reversed by a vasopressin antagonist injected systemically, but was totally abolished by systemic α-adrenergic blockade with phentolamine. These findings suggest that sodium can cause hypertension by direct stimulation of the central sympathetic nervous system without participation of peripheral mechanisms such as fluid volume expansion or alteration of the vascular wall.

The contribution of the renin-angiotensin system to limb vasoregulation in patients with heart failure: observations during orthostasis and α-adrenergic blockade

1. In patients with congestive heart failure, both the sympathetic nervous system and renin-angiotensin system are often stimulated. In order to assess the contribution of the renin-angiotensin system to limb vascular resistance, the forearm haemodynamic response to captopril was studied in 13 patients with heart failure. 2. Seven subjects were studied while supine and during 60 degrees head-up tilt. To eliminate alpha-adrenergic effects, six additional patients with heart failure were pretreated with intra-arterial phentolamine and then given captopril. Venous occlusion plethysmography was used to determine forearm blood flow and forearm vascular resistance. 3. Tilt did not significantly increase pretreatment plasma renin activity or plasma noradrenaline concentration, nor did it decrease forearm blood flow. Furthermore, captopril did not alter forearm vascular resistance during supine or upright posture. During the phentolamine infusion, however, captopril reduced forearm vascular resistance by 19% (P < 0.05). 4. Despite increased plasma renin activity, captopril did not cause forearm vasodilatation during supine or upright posture in these patients with heart failure. When the contribution of the sympathetic nervous system was eliminated, captopril decreased forearm vascular resistance. Therefore, in patients with congestive heart failure, the sympathetic nervous system is important in limb vasoregulation, and the contribution of the renin-angiotensin system is apparent only after alpha-adrenergic blockade.