Autonomic nervous control of the circulatory system in the air-breathing fish Channa argus

The control of the cardiovascular system with particular emphasis on the regulation of blood distribution in the gills and air-breathing organ was studied in the air-breathing teleost Channa argus. Perfused head preparations were used in addition to experiments with isolated strip preparations of arteries and heart chambers. The distribution of adrenergic nerves was investigated using Falck-Hillarp fluorescence histochemistry. This preliminary study shows an adrenergic control system composed of chromaffin cells and adrenergic nerves similar to that found in other teleosts investigated, although the systemic arteries (coeliac artery, dorsal aorta and the vasculature of the air-breathing organ) appear to lack an adrenergic innervation. The reactions of isolated artery strip preparations to acetylcholine and adrenaline resemble those seen in other teleosts, and there is a prominent inhibitory effect of L-isoprenaline suggestive of arterial beta-adrenoceptors. The general vascular resistance of the gill apparatus-air-breathing organ increases in response to acetylcholine or adrenaline, and there is a redistribution of perfusion flow from the air-breathing organ circuit (anterior venous outflow from the first and second pair of gills and the air-breathing organ) to the general systemic circuit (dorsal aortic outflow from the third and fourth pair of gills). Stimulation of the vagal branch entering the air-breathing organ mimics the effects of acetylcholine or adrenaline. This innervation is probably non-adrenergic since no adrenergic nerve fibres could be demonstrated in the vasculature of the air-breathing organ using the histochemical technique. An adrenergic control of the vasculature of the air-breathing organ is not likely, since the concentration of adrenaline needed to affect the vasculature is not reached in the plasma even during "stress".     

The action of ADP ribose on the mechanical and bioelectrical activity of the frog heart]

In the frog isolated heart, cyclic perfusion of ADP-ribose induced a dose-dependent decrease in the heart rate and the contraction force, a decrease in the AP duration as well as in the rate of rise in the sinus node. It also shortened the atrial AP and exerted no significant effect upon multicellular ventricular preparations. In conditions of systemic administration in unanesthetised frogs, the ADP-ribose induced a reversible increase in the heart rate due, probably, to a sympathetic effect.     

Systemic circulatory effects of pentagastrin

Effects of pentagastrin on systemic circulation were studied in anesthetized cats. Systemic arterial, central venous and portal pressure were monitored with electromanometers and blood flow through the superior mesenteric artery, common carotid artery, femoral artery and ascending aorta were measured with an electromagnetic blood flow meter. Pentagastrin injected intravenously at a doses of 2.0, 4.0 and 8.0 micrograms/kg induced a dose-dependent fall in arterial pressure, heart rate and cardiac output, increased mesenteric blood flow, decreased common carotid artery blood flow, did not change femoral artery blood flow and slightly rose central venous pressure. Atropine blocked observed effects. After repeated injections of the peptide, tachyphylaxis quickly developed. The obtained results indicate that pentagastrin influences general hemodynamics probably via interaction with cholinergic receptors.     

Influence of vasoactive intestinal polypeptide (VIP) on splanchnic and central hemodynamics in healthy subjects

The influence of VIP, a potent vasodilator, on central hemodynamics, splanchnic blood flow and glucose metabolism was studied in six healthy subjects. Teflon catheters were inserted into an artery, a femoral vein and a right-sided hepatic vein. A Swan-Ganz catheter was introduced percutaneously and its tip placed in the pulmonary artery. Determinations of cardiac output, systemic, pulmonary arterial and hepatic venous pressures as well as splanchnic blood flow were made in the basal state and at the end of two consecutive 45 min periods of VIP infusion at 5 and 10 ng/kg/min, respectively. Arterial blood samples for analysis of glucose, FFA, insulin and glucagon were drawn at timed intervals. VIP infusion at 5 ng/kg/min resulted in an increase in cardiac output (55%) and heart rate (25%) as well as a reduction in mean systemic arterial pressure (15%) and vascular resistance (45%). With the higher rate of VIP infusion heart rate tended to rise further while cardiac output and arterial pressure remained unchanged. At 15 min after the end of VIP infusion the above variables had returned to basal levels. Splanchnic blood flow and free hepatic venous pressure did not change significantly. Arterial concentrations of glucose, FFA, insulin and glucagon increased during VIP infusion. At 15 min after the end of infusion the glucose levels were still significantly higher than basal (20%). Net splanchnic glucose output did not change in response to VIP infusion. It is concluded that VIP exerts a potent vasodilatory effect resulting in augmented cardiac output and lowered systemic blood pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

The principle of laplace and scaling of ventricular wall stress and blood pressure in mammals and birds

Maximum left ventricular wall stress is calculated at end-diastolic volume and systemic arterial diastolic blood pressure, according to a thick-walled model for the principle of Laplace. Stress is independent of body mass and averages 13.9 kPa (+/-2.3; 95% confidence interval) in 24 species of mammals weighing 0.025-4,000 kg and 15.5 kPa (+/-4.7) in 12 birds weighing 0.014-110 kg. Birds have higher arterial blood pressures and larger hearts than mammals. Systolic and diastolic arterial blood pressures increase with body mass according to M(0.05) in mammals, and heart mass increases according to M(1.06) in the same species, further supporting the principle. However, blood pressure in birds is independent of body mass, and heart mass scales isometrically. End-diastolic stress values, calculated according to Laplace, are about one-third of peak stresses recorded in isolated mammalian myocardial preparations.     

Direct effects in vivo of angiotensins I and II on the canine sinus node.

The chronotropic responses to angiotensins I and II (5 micrograms in 1 mL Tyrode's solution) injected into the sinus node artery were assessed before and after the intravenous administration of captopril (2 mg/kg) and saralasin (20 micrograms/kg) in anaesthetized dogs. The effects of angiotensin II given intravenously were also observed. The animals (n = 8) were vagotomized and pretreated with propranolol (1 mg/kg, i.v.) to prevent baroreceptor-mediated responses to increases in blood pressure. Injection of angiotensin I into the sinus node artery induced significant increases in heart rate (114 +/- 6 vs. 133 +/- 6 beats/min) and in systemic systolic (134 +/- 13 vs. 157 +/- 14 mmHg; 1 mmHg = 133.3 Pa) and diastolic (95 +/- 10 vs. 126 +/- 13 mmHg) blood pressures. Similar results were obtained when angiotensin II was injected into the sinus node artery, but intravenous injection induced changes in systolic (138 +/- 8 vs. 180 +/- 25 mmHg) and diastolic (103 +/- 8 vs. 145 +/- 20 mmHg) blood pressures only. Captopril induced a significant decrease in systolic (118 +/- 11 vs. 88 +/- 12 mmHg) and diastolic (84 +/- 9 vs. 59 +/- 9 mmHg) blood pressures without affecting the heart rate (109 +/- 6 vs. 106 +/- 6 beats/min). Saralasin produced a significant increase in systolic (109 +/- 7 vs. 126 +/- 12 mmHg) blood pressure only. Increments in heart rate and systolic and diastolic blood pressures in response to angiotensins I and II were, respectively, abolished by captopril and saralasin. It was concluded that angiotensin II has, in vivo, a direct positive chronotropic effect that can be blocked by saralasin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological basis for preferential uptake of D-alpha-aminoadipate over the L-isomer by Alcaligenes denitrificans.

Alcaligenes denitrificans, pre-incubated with D-alpha-aminoadipate and assayed for L-isomer uptake without removal of extracellular D-isomer, exhibits a reduced rate of uptake and a reduced level at which steady state is achieved. During D- or L-isomer uptake, intracellular alpha-aminoadipate is exclusively the L-configuration. These data are consistent with an intracellular, mediated reduction in L-isomer uptake as the physiological basis for preferential D-alpha-aminoadipate uptake by A. denitrificans growing on racemic alpha-aminoadipate. Translocated D-alpha-aminoadipate is rapidly metabolized to form an L-isomer pool which subsequently reduces the rate of L-isomer uptake and the level at which steady state occurs resulting in a preferred D-isomer uptake. Competitive inhibition of L-alpha-aminoadipate uptake by the D-isomer or a difference in the maximum rates of uptate uptake is an inducible process expressed only in the presence of that compound and while uptake of L-alpha-animoadipate is also inducible there is a low rate of constitutive uptake. While L-alpha-aminoadipate uptake occurs against a concentration gradient, uptake of the D-isomer is not against a gradient. D- and L-isomer uptake are active processes since both are inhibited by azide, cyanide and 2,4-dinitrophenol.     

Effect of compound D-600 (methoxyverapamil) on gluconeogenesis and on acceleration of the process by alpha-adrenergic stimuli in rat kidney tubules.

1. Tubule fragments were isolated from renal cortex of fed rats and glucose formation was measured after incubation with 5 mM-sodium lactate. 20 Compound D-600 (10-100 microM) decreased gluconeogenesis from lactate. This inhibition of the process by compound D-600 increased with increasing extracellular Ca2+ concentration, was overridden by noradrenaline and diminished by starvation for 24 h. 3. Inhibition of lactate-supported gluconeogenesis by compound D-600 was not prevented by the alpha 1-adrenoceptor antagonist thymoxamine. 4. Compound D-600 had little effect on gluconeogenesis from 2-oxoglutarate and increased gluconeogenesis from succinate. 5. Compound D-600 opposed stimulation of gluconeogenesis by noradrenaline or oxymetazoline (a selective alpha-adrenoceptor agonist) in a manner suggesting that compound D-600 is an alpha-adrenoceptor blocker. Oxymetazoline was more sensitive than noradrenaline to blockade by both compound D-600 and by the conventional alpha-adrenoceptor antagonist phentolamine. Noradrenaline became more sensitive to blockade by compound D-600 when extracellular Ca2+ was decreased. 6. Compound D-600 did not block stimulation of gluconeogenesis by angiotensin or cyclic AMP.     

Vasodilatory and diuretic actions of alpha-human atrial natriuretic polypeptide (alpha-hANP)

Vascular and diuretic actions of synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) were studied using anesthetized dogs and isolated canine arterial strip preparations. alpha-hANP, when given intra-arterially or intravenously, dilated the renal artery more selectively than the vertebral, femoral, common carotid and coronary arteries. alpha-hANP selectively relaxed the high K+-contracted renal artery strip as compared with the basilar, coronary and femoral arterial strips. Intravenous alpha-hANP also increased urine volume and urinary excretion of electrolytes at doses, at which it increased renal blood flow and lowered systemic blood pressure without changing heart rate. It is concluded that alpha-hANP has a vasodilatory property relatively specific for the renal artery, and that it possesses diuretic, natriuretic, kaliuretic, magnesiuretic, calciuretic and chloruretic activities concomitantly with a definite hypotensive activity.     

Effects of intracerebroventricularly injected glucagon-like peptide-1 on cardiovascular parameters; role of central cholinergic system and vasopressin

We aimed to investigate the effects of intracerebroventricularly (i.c.v.) injected glucagon-like peptide-1 (GLP-1) on blood pressure and heart rate, and whether central cholinergic system and vasopressinergic system play roles in these effects. Male Wistar albino rats were used throughout the experiments. Blood pressures and heart rates were observed before and for 30 min following drug injections. i.c.v. GLP-1 (100, 500 and 1000 ng/10 microl) caused a dose-dependent increase in both blood pressure and heart rate. Nicotinic receptor antagonist mecamylamine (25 microg/10 microl, i.c.v.) and muscarinic receptor antagonist atropine (5 microg/10 microl, i.c.v.) prevented the stimulating effect of GLP-1 on blood pressure. The effect of GLP-1 on heart rate was blocked only by mecamylamine. The V1 receptor antagonist of vasopressin (B-mercapto B, B-cyclopentamethylenepropionyl, O-Me-Tyr,Arg)-vasopressin (10 microg/kg), that was applied intraarterially, only prevented the effect of GLP-1 on blood pressure, but did not show any effect on heart rate. Our data indicate that i.c.v. GLP-1 increases blood pressure and heart rate, and stimulation of central nicotinic and partially muscarinic receptors and vasopressinergic system play a role in the effects of i.c.v. GLP-1 on blood pressure. The effect of GLP-1 on heart rate may be partially due to stimulation of central nicotinic receptors.     

Effect of atrial natriuretic factor on arterial blood pressure and frequency of heart contraction in rats with genetically determined hypertension and in normotensive rats

An effect of peptide released by the heart atria of mammals and called the atrial natriuretic factor (ANF) on blood pressure and heart contractions was studied in rats with genetically determined arterial hypertension (SHR) and in normotensive Wistar-Kyoto rats (WKY). Nine male SHR rats and 11 male WKY rats, aged between 12 and 16 weeks, were given normal saline infusion for 30 minutes through implanted catheters to both ulnar vein and artery. Then, an infusion of ANF at the rate of 0.3 microgram/kg per hour followed for 35 minutes. An infusion of ANF produces significant decrease in the mean arterial blood pressure, systolic and diastolic pressures without significant effect on pulse pressure and heart contractions. AFN infusion with the same rate did not produce any significant differences in the arterial blood pressure and heart contractions in Wistar-Kyoto rats. The obtained results suggest that ANF may play a role in pathogenesis of the arterial blood hypertension.     

Twenty-four-hour blood pressure control: an intraarterial review.

Intraarterial blood pressure monitoring has shown the circadian rhythm of blood pressure control. Blood pressures tend to be highest in the morning before falling gradually during the day to a nadir at 3:00 a.m. There is a slight rise in the late afternoon that may correspond to patients' attendance at hospital for calibration of the equipment. There is a small rise in the blood pressure before awakening, and after arousal there is a rise in blood pressure to the peak level of the morning. In this article, we examine the effect of a variety of antihypertensive agents on this rhythm. In general, beta-adrenoceptor blockers appear to have less effect on nocturnal blood pressure and surge in pressure after arousal, while vasodilators, particularly alpha-adrenoceptor blockers, have a pronounced effect. These findings indicate that the rise in blood pressure before awakening and the rapid rise upon arousal appear to be due to increased alpha-adrenoceptor activity.     

Effect of enhanced red blood cell aggregation on blood flow resistance in an isolated-perfused guinea pig heart preparation

The role of red blood cell (RBC) aggregation as a determinant of in vivo blood flow is still unclear. This study was designed to investigate the influence of a well-controlled enhancement of RBC aggregation on blood flow resistance in an isolated-perfused heart preparation. Guinea pig hearts were perfused through a catheter inserted into the root of the aorta using a pressure servo-controlled pump system that maintained perfusion pressures of 30 to 100 mmHg. The hearts were beating at their intrinsic rates and pumping against the perfusion pressure. RBC aggregation was increased by Pluronic (F98) coating of RBC at a concentration 0.025 mg/ml, corresponding to about a 100% increment in RBC aggregation as measured by erythrocyte sedimentation rate. Isolated heart preparations were perfused with 0.40 l/l hematocrit unmodified guinea pig blood and with Pluronic-coated RBC suspensions in autologous plasma. At high perfusion pressures there were no significant differences between the flow resistance values for the two perfusates, with differences in flow resistance only becoming significant at lower perfusion pressures. These results can be interpreted to reflect the shear dependence of RBC aggregation: higher shear forces associated with higher perfusion pressures should have dispersed RBC aggregates resulting in blood flow resistances similar to control values. Experiments repeated in preparations in which the smooth muscle tone was inhibited by pre-treatment with papaverine indicated that significant effects of enhanced RBC aggregation could be detected at higher perfusion pressures, underlining the compensatory role of vasomotor control mechanisms.     

Comparison of norepinephrine and serotonin vasoconstriction of the rat isolated testicular subcapsular artery at physiological and elevated transmural pressures.

This laboratory has previously described an in vitro preparation showing that the isolated testicular subcapsular artery of the adult rat has a novel triphasic transmural pressure-diameter myogenic response curve consisting of vasodilatation from 20 to 40 mm Hg, vasoconstriction from 40 to 100 mm Hg, and vasodilatation from 100 to 180 mm Hg, suggesting that the myogenic response of this artery between 40 and 100 mm Hg may have an important role in the autoregulation of the testicular blood supply. In the present studies, a 10-mm length of the adult rat isolated testicular subcapsular artery was cannulated and pressurized by an adjustable-height reservoir. External and internal arterial diameters were measured by a digital filar micrometer eyepiece. Dose-response curves for norepinephrine and serotonin were generated in a double-bath artery chamber at transmural pressures of 70 and 140 mm Hg, using half of the same artery for each pressure. Norepinephrine (3 x 10(-8) to 1 x 10(-5) M) produced a dose-dependent vasoconstriction at 70 mm Hg, with the highest dose causing a 31.4% decrease in lumen cross-sectional area (p < 0.05). Serotonin (3 x 10(-8) to 1 x 10(-6) M) produced a stronger dose-dependent vasoconstriction at 70 mm Hg, with the highest dose causing a 72.7% decrease in lumen cross-sectional area (p < 0.05). In marked contrast, the same concentration of norepinephrine and serotonin were found to have no statistically significant effect on the lumen cross-sectional area of the isolated testicular subcapsular artery at a transmural pressure of 140 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular effects of matrine isolated from the Chinese herb Shan-dou-gen

Matrine, a pure compound isolated from the Chinese herb Shan-don-Gen (Sophora subprostrata), was studied for its effects on the cardiovascular system of the rat. Intravenous injections of matrine at doses from 5 mg to 20 mg/kg body weight exhibited dose-dependent hypotensive and bradycardiac effects. These effects lasted only 1 to 3 min. In the isolated atria and ventricle preparations, matrine at doses from 50 micrograms to 200 micrograms/ml increased the amplitudes of spontaneous contraction of the atria and electrically induced contraction of the ventricle, whereas the frequency of the spontaneous beating of the atria was reduced. The dose-dependent effects of matrine on the isolated preparations persisted as long as the compound was present. Tachyphylaxis was not observed with repeated applications of this compound to the isolated preparations. The positive inotropic effects on both atria and ventricle and the negative chronotropic effect on spontaneous beating of the atria by matrine were not blocked by diphenhydramine, atropine, phenoxybenzamine, propranolol, trifluoperazine, or methysergide. In contrast, verapamil significantly reduced the positive inotropic effect of matrine on the ventricle. In the isolated aortic strip preparation, matrine at a dose of 200 micrograms/ml led to a slight increase in muscle tone. The same dose of matrine induced a 35% increase of perfusion pressure in the hindleg perfusion model. These results suggest that the in vivo transient hypotensive effect of matrine is likely associated with a decrease in heart rate itself, since positive inotropic effects on both the atria and the ventricle, and vasoconstriction of some vascular beds could not be the cause of hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence that neurotensin mediates postprandial intestinal hyperemia in the python, Python regius

Digestion of large meals in pythons produces substantial increases in heart rate and cardiac output, as well as a dilation of the mesenteric vascular bed leading to intestinal hyperemia, but the mediators of these effects are unknown. Bolus intra-arterial injections of python neurotensin ([His(3), Val(4), Ala(7)]NT) (1 - 1,000 pmol/kg) into the anesthetized ball python Python regius (n = 7) produced a dose-dependent vasodilation that was associated with a decrease in systemic pressure (P(sys)) and increase in systemic blood flow (Q(sys)). There was no effect on pulmonary pressure and conductance. A significant (P < 0.05) increase in heart rate (f(H)) and total cardiac output (Q(tot)) was seen only at high doses (>30 pmol/kg). The systemic vasodilation and increase in Q(tot) persisted after beta-adrenergic blockade with propranolol, but the rise in f(H) was abolished. Also, the systemic vasodilation persisted after histamine H(2)-receptor blockade. In unanesthetized pythons (n = 4), bolus injection of python NT in a dose as low as 1 pmol/kg produced a significant increase in blood flow to the mesenteric artery (177% +/- 54%; mean +/- SE) and mesenteric conductance (219% +/- 74%) without any increase in Q(sys), systemic conductance, P(sys), and f(H). The data provide evidence that NT is an important hormonal mediator of postprandial intestinal hyperemia in the python, but its involvement in mediating the cardiac responses to digestion may be relatively minor.     

Human alpha- and beta-CGRP and rat alpha-CGRP are coronary vasodilators in the rat

The effects of the recently described human alpha-calcitonin gene-related peptide (CGRP), human beta-CGRP and rat alpha-CGRP have been compared with those of the vasodilator sodium nitroprusside, on the rat and rabbit isolated heart. Hearts were perfused at constant flow and [Arg8]-vasopressin was used to increase coronary perfusion pressure. In the rat heart, the order of potency for evoking cumulative dose-dependent falls in perfusion pressure was human beta-CGRP greater than rat alpha-CGRP greater than human alpha-CGRP greater than sodium nitroprusside. In the same preparations the three CGRPs (but not sodium nitroprusside) elicited cumulative dose-related increases in heart rate. In the rabbit heart the order of potency for vasodilatation was rat alpha-CGRP greater than human alpha-CGRP greater than sodium nitroprusside. In marked contrast to results from the rat, neither rat alpha-CGRP nor human alpha-CGRP altered heart rate in the rabbit isolated heart. These results show that human alpha- and beta-CGRP and rat alpha-CGRP are vasodilators in the coronary vasculature, but that there is species variation as CGRP had a positive chronotropic effect in the rat heart but not in the rabbit heart.     

A method for calculation of human systolic and diastolic blood pressures using an elastic reservoir theory of the systemic arterial system,and some clinical and physiological applications

Two equations have been developed that describe the interrelationship of the clinically measurable variables of the human systemic arterial system. An approximation method is given for their simultaneous solution for systolic and diastolic pressures in terms of heart rate, cardiac output, total peripheral resistance, and aortic distensibility. In this way, blood pressures were calculated for various clinically important and didactically useful situations. The effects on systolic and diastolic pressures due to changing either cardiac output or peripheral resistance or heart rate or aortic distensibility alone are shown. The effects on pulse pressure of varying cardiac output and peripheral resistance while holding mean arterial pressure constant are demonstrated. Compensatory mechanisms in hypertension and exercise are explored. Opinions and conclusions contained in this report are those of the author. They are not to be construed as necessarily reflecting the views or the endorsement of the Navy Department.     

Diabetes-induced changes of nitric oxide influence on the cardiovascular action of secretin

The modulation by condition of the lack or the excess of nitric oxide (NO) on cardiovascular action of secretin in diabetic rats was investigated. In vitro the isolated heart function and in vivo, the systolic (SBP), diastolic (DSP) blood pressure and heart rate (HR) were measured. Secretin evoked inotropic positive effect and increased coronary outflow (CO), in vivo did not increase systemic pressure and the highest dose of the peptide increased the heart rate. NO synthase inhibitor, N(G) nitro-L-arginine methyl ester (L-NAME) deeply increased the systemic pressure and in vitro decreased coronary outflow. L-arginine and sodium nitroprusside (SNP) did not influence the isolated heart function and in vivo decreased the systemic pressure. L-NAME preserved the inotropic positive effect of secretin and the increase of the coronary outflow. In vivo co-administration of L-NAME+secretin evoked hypotensive effect and abolished the increase of the heart rate after the highest dose of the peptide. L-arginine abolished inotropic positive effect of the peptide and the increase of coronary outflow. In vivo co-administration of these substances caused hypotension and attenuated the increase of the heart rate after the highest dose of secretin. Co-injection of SNP and secretin preserved the inotropic effect of secretin and abolished the increase of the coronary outflow. In vivo infusion of SNP+secretin evoked hypotension and similarly to L-arginine, SNP abolished tachycardia induced by the highest dose of secretin. Both the lack and the excess of nitric oxide changed the cardiovascular action of secretin in diabetic rats.     

Alpha-adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in experimental diabetes mellitus.

This study tested whether alpha-adrenoceptor-mediated coronary vasoconstriction is augmented during exercise in diabetes mellitus. Experiments were conducted in dogs instrumented with catheters in the aorta and coronary sinus and with a flow transducer around the circumflex coronary artery. Diabetes was induced with alloxan monohydrate (n = 8, 40 mg/kg i.v.). Arterial plasma glucose concentration increased from 4.7 +/- 0.2 mM in nondiabetic, control dogs (n = 8) to 21.4 +/- 1.9 mM 1 wk after alloxan injection. Coronary blood flow, myocardial oxygen consumption (MVo(2)), aortic pressure, and heart rate were measured at rest and during graded treadmill exercise before and after infusion of the alpha-adrenoceptor antagonist phentolamine (1 mg/kg iv). In untreated diabetic dogs, exercise increased MVo(2) 2.7-fold, coronary blood flow 2.2-fold, and heart rate 2.3-fold. Coronary venous Po(2) fell as MVo(2) increased during exercise. After alpha-adrenoceptor blockade, exercise increased MVo(2) 3.1-fold, coronary blood flow 2.7-fold, and heart rate 2.1-fold. Relative to untreated diabetic dogs, alpha-adrenoceptor blockade significantly decreased the slope of the relationship between coronary venous Po(2) and MVo(2). The difference between the untreated and phentolamine-treated slopes was greater in the diabetic dogs than in the nondiabetic dogs. In addition, the decrease in coronary blood flow to intracoronary norepinephrine infusion was significantly augmented in anesthetized, open-chest, beta-adrenoceptor-blocked diabetic dogs compared with the nondiabetic dogs. These findings demonstrate that alpha-adrenoceptor-mediated coronary vasoconstriction is augmented in alloxan-induced diabetic dogs during physiological increases in MVo(2).