Characterization of vascular dopamine receptors in the gastric circulation of the rabbit.

An in vivo model is presented for studying the vasodilator effect of dopamine on the gastric vascular bed of the anesthetized rabbit. Dopamine was injected into the common hepatic artery simultaneously measuring the blood flow through the left gastric artery at constant perfusion pressure. The vasoconstrictor response to dopamine was blocked by pretreatment with phenoxybenzamine (0.5 mg/kg i.a.). Dopamine dilated the gastric vascular bed dose-dependently with an average ED50 of 15 nmol. Apomorphine caused vasodilation with an ED50 of 38.8 nmol; the maximum response was significantly lower than dopamine. (-)Isoproterenol was ineffective. cis-Flupentixol (3.5 and 7.0 mumol/kg i.v.) and (+)butaclamol (3.0 mumol/kg i.v.), but not trans-flupentixol (7.0 mumol/kg i.v.) and (-)butaclamol (6.0 mumol/kg i.v.) shifted the dopamine dose-response curve to the right in a parallel fashion, indicating competitive antagonism. Haloperidol, bulbocapnine, and sulpiride also acted as competitive inhibitors of dopamine-induced vasodilation. The antagonists inhibited the dopamine-induced vasodilation in the following order of potency: (+)butaclamol greater than cis-flupentixol greater than haloperidol greater than bulbocapnine greater than sulpiride. The results suggest that the vascular dopamine receptors in the stomach of the rabbit resemble the DA1-receptors in the mesenteric vascular bed of dogs.

Blood flow redistribution by dopamine in the feline gastrointestinal tract.

The effect of intravenous infusion of dopamine (10 and 25 micrograms X kg-1 X min-1 consecutively) on visceral blood flow distribution was examined in anesthetized cats using the microsphere technique and electromagnetic flowmetry. Arterial blood pressure did not change in response to dopamine infusion, but blood flow through the superior mesenteric artery, and blood flow in the mucosa-submucosa of the gastric antrum and various gut segments increased significantly. During infusion of the high dose the increase was most marked in the mucosa-submucosa of the antrum (+355%) and distal colon (+371%). By contrast, blood flow decreased in the muscularis-serosa of the gut segments investigated, in the spleen, pancreas, and the hepatic arterial bed. The increase in blood flow through the superior mesenteric artery was blocked by the dopamine antagonist bulbocapnine (10 mg/kg i.v.). The results suggest that the receptors mediating the dopamine-induced vasodilation in the gastrointestinal tract are located in the resistance vessels of the mucosa-submucosa.

Dopamine produces vasodilation in specific regions and layers of the rabbit gastrointestinal tract.

The effect of intravenous dopamine infusion (25 and 60 micrograms per kg and min consecutively) on blood flow distribution in the splanchnic region of anesthetized rabbits was studied applying the microsphere technique. During infusion of the low dose, blood flow increased most markedly in the stomach, less in the pancreas, jejunum and descending colon, and decreased in the spleen. In the stomach the increase was confined to the mucosa-submucosa. Raising the dose of dopamine resulted in a slight fall of arterial blood pressure, a further increase in blood flow through the mucosa-submucosa of the gastric fundus (+493 % as against control), but not through the other tissues studied. In another series, blood flow through the left gastric artery was measured with an electromagnetic flowmeter. The infusion of dopamine produced a dose-dependent increase in regional blood flow, which was inhibited by the dopamine antagonist bulbocapnine. Furthermore, the control blood flow was transiently decreased, and resistance to flow was increased by bulbocapnine. The results indicate that the dopamine-induced vasodilation in the gastrointestinal tract of the rabbit is largely restricted to the gastric circulation and suggest that specific receptors mediating this vasodilation are located in the mucosa-submucosa. It is hypothesized that endogenous dopamine functions as a vasodilatory tissue hormone in the gastric mucosa of the rabbit.

Regional blood flow during paraoxon infusion in rabbits.

In anaesthetized and artificially ventilated rabbits an intravenous infusion of paraoxon (0.8 mg/kg) was given over 30 min. The effects on cardiac output, blood flow to various vascular beds, and on the mass discharge of the postganglionic sympathetic efferents to the spleen and kidney were monitored. Immediately following paraoxon infusion atropine (0.5 mg/kg) was injected intravenously. Within 20 min of commencing the infusion signs of increased cholinergic stimulation were observed. Between the 20th and 25th min mean arterial blood pressure, heart rate, and cardiac output fell markedly. Even before arterial blood pressure fell total peripheral resistance and regional resistance to flow through the subclavian and coeliac arteries increased significantly, whereas resistance was below control, increased regional resistance being found only in the vascular beds of the subclavian and splenic arteries. The activity in the splenic sympathetic efferents increased, while the activity in the renal efferents was sharply reduced. While an effective antidote, atropine elicited transient intestinal vasodilation and a further transient decrease in total peripheral resistance. These and other results suggest that muscarinic mechanisms are mainly responsible for the paraoxon-induced changes in regional blood flow and regional sympathetic activity. The vasodilatory effect of atropine in the intestine was probably due to a local autoregulatory mechanism.

Cardiovascular reflexes controlling regional sympathetic outflow during coronary artery occlusion.

In anesthetized rabbits, sympathetic activity was recorded in efferents to the skin of the ear (ESA), to the hindlimb muscles (MSA), splanchnic region (SSA), adrenals (ASA), and kidneys (KSA) in response to occlusion of the left circumflex coronary artery. Coronary occlusion caused an average decrease of mean arterial blood pressure by 18%. MSA and SSA increased, ESA decreased, and ASA, KSA, and heart rate either decreased or increased. In response to occlusion after cervical vagotomy, the fall in arterial mean pressure (11%) and the increases in MSA and SSA were less than those with intact vagal nerves. ASA and KSA increased, ESA decreased, and heart rate did not change significantly. In response to occlusion after selective sinoaortic denervation, arterial mean pressure dropped more than before denervation (32%); heart rate fell slightly. The increases in MSA and SSA were almost completely abolished, but in some rabbits irregular bursts were observed in KSA. The results suggest that a vagal depressor reflex dominated the arterial baroreflex in the control of the sympathetic outflow to the kidneys and adrenals without apparently influencing the outflow to the other investigated regions. There are some indications that excitation of cardiac receptors with sympathetic afferents contributed to the changes of ESA and KSA.

Dopamine-induced diuresis in the cat without changes in renal hemodynamics.

The effects of intravenous (i.v.) and intraarterial (i.a.) injection and infusion of dopamine (DA) on renal hemodynamics, regional sympathetic activity and kidney function were investigated in anaesthetized cats. In response to the i.v. bolus injection of DA (25 microgram/kg), mean arterial blood pressure (MABP) was increased by 19.7%, renal blood flow (RBF) by 16.6%, and regional sympathetic discharges were inhibited. The principal effect of i.a. bolus injection of DA into the renal artery was vasoconstriction. Vasodilation was observed neither after lower doses of DA nor after pretreatment with phenoxybenzamine. During continuous i.v. infusion of 10 microgram DA kg-1 min-1 MABP, RBF, renal sympathetic discharges and glomerular filtration rate (GFR) did not change, whereas urine volume was increased by 120.5%, sodium excretion by 99.7%, chloride excretion by 143.2%, and potassium excretion by 31.9%. Urine osmolality was decreased and osmolal clearance increased. Raising the DA dose to 25 microgram kg-1 min-1 resulted in a fall of GFR, but the diuretic response was not significantly different from that of the low dose. Bulbocapnine (6 mg/kg i.v.) antagonized the DA-induced diuresis. In conclusion, the diuretic effect of DA in the cat is not dependent on a change in RBF, GFR or renal sympathetic activity. This suggests that a tubular site of action is primarily responsible for DA diuresis.

Regional pre- and postganglionic sympathetic activity during experimental paraoxon poisoning.

The effects of 0.4 or 0.8 mg paraoxon/kg i.v. on circulation and regional pre- and postganglionic sympathetic activity were studied in anaesthetized rabbits. At both doses, the discharges of the preganglionic efferents increased slowly, whereas the changes in activity of postganglionic efferents differed. Concomitantly with a transient initial rise in blood pressure a temporary increase of discharges to the skeletal muscles and to the intestine was observed which is attributed to spontaneous firing of the regional ganglionic cells. After injection of 0.4 mg/kg there occasionally occurred a second pressor reaction conditioned by enhancement of preganglionic activity and facilitated transmission in certain sympathetic ganglia. After injection of the higher dose, postganglionic activity generally decreased except for the discharges of gastrointestinal efferents, which increased. Arterial blood pressure, cardiac output and total peripheral resistance fell markedly. A shock syndrome occurred which could be controlled by atropine injection if timely. From the results it was concluded that the higher dose of paraoxon blocked synaptic transmission in the paravertebral ganglia of the sympathetic trunk, and facilitated impulse transmission in the prevertebral abdominal ganglia.

Arterial baroreceptor function in differential cardiovascular adjustments induced by central thermal stimulation.

Dogs were anesthetized with sodium pentobarbital, relaxed with succinyl choline and were kept under artificial ventilation. Both carotid bifurcations were denervated and the Vagus nerves were cut in the neck. Regional blood flow in the skin and the intestine, cardiac output, heart rate and arterial pressure were determined before, during and after spinal cord heating and cooling. Further experiments were performed in which, in addition, sympathetic effects on the heart were excluded by exstirpation of the caudal cervical and stellate ganglia or by beta-receptor blockade. The cardiovascular responses were compared with those obtained in a preceding investigation from dogs with intact baroreceptors and vagus nerves. As in intact dogs, appropiate thermoregulatory adjustments of skin blood flow were induced by thermal stimulation of the spinal cord after baroreceptor denervation and vagotomy. However, blood pressure homeostasis was lost. The pattern of cardiovascular ajustments during heating consisted in cutaneous vasodilatation intestinal vasoconstriction and, due to sympathetic activation an increase of heart rate and cardiac output. This pattern was qualitatively identical with that intact animals. During spinal cord cooling the cardiovascular response pattern consisted in cutaneous vasoconstriction, intestinal vasoconstriction and, depending on cooling intensity, a reduced or unchanged sympathetic influence on the heart. This pattern differed considerably from what in intact animals but basic features were still present as indicated by opposite changes of cardiac and vascular sympathetic tone during cooling. It is concluded that the baroreceptor signals play no primary role in the generation of differential vasomotor responses under the present experimental conditions. This confirms assumptions made on the basis of observations in animals with intact baroreceptor input. However, baroreceptor signals contribute significantly to blood pressure homeostasis which is normally maintained during spinal thermal stimulation.