Effect of angiotensin-induced hypertension on rat coronary arteries and myocardium.

Acute hypertension has been produced in rats by the intravenous infusion of angiotensin amide for 4 hours. Both control and hypertensive animals were injected intravenously prior to sacrifice with either horseradish peroxidase (HRP) or colloidal carbon. Epicardial arteries and blocks of ventricular myocardium containing intramyocardial arteries and arterioles have been processed for electron microscopy. HRP appears to penetrate the endoethelium of epicardial arteries from control animals within vesicles that bypass endothelial junctions and empty into interendoethelial clefts. Peroxidase does not traverse the endothelium of intramural arteries and arterioles of controls over the 10-minute period of observation. There is acceleration of lateral vesicular transport in the endothelium of epicardial arteries after angiotensin infusion and direct permeation of interendothelial clefts of intramural arterial vessels. Medial fragmentation and more extensive necrosis are observed in intramyocardial but not in epicardial arterial vessels. Foci of myocardial damage resembling irreversible ischemic or anoxic injury followed by reflow are described. It is suggested that the increased permeability of epicardial arteries may be due to elevated pressure, while the altered permeability and vascular lesions of intramural arteries and arterioles are more readily attributable to the vasoconstriction produced by angiotension. The vascular and myocardial lesions are also discussed in relation to the regional actions of angiotensin on the coronary circulation and known effects of this vasoactive peptide on myocardium.     

Ultrastructure of coronary arteries and myocardium in experimental hypertension

The ultrastructure of coronary arteries and myocardium has been examined after 1–4 weeks of experimental hypertension produced in Wistar-Kyoto rats by unilateral renal artery constriction. Upon sacrifice blocks of ventricular myocardium were processed for light and electron microscopy. Two types of medial necrosis are observed in epicardial arteries: one involving elongated smooth muscle cells throughout the media and the other localized to the outer layers of the vessel wall. Some of the epicardial and intramyocardial arteries exhibit hyperplastic lesions characterized by smooth muscle cells in the subendothelial space. Medial smooth muscle cells of small intramyocardial arteries also exhibit contraction, fragmentation and necrosis. Plasma, cells and fibrin accumulate in the subendothelial space of intramyocardial arteries. Discrete areas of myocardial injury of variable severity are present in the subendocardium of the left ventricle. The vascular lesions in epicardial and intramyocardial arteries are related to the severity of blood pressure elevation and the vasoconstrictor actions of angiotensin II, while the foci of myocardial damage are consistent with ischemic or anoxic injury.     

Alpha-adrenoceptor-mediated penile erection in dogs: in vivo and in vitro observations.

We have evaluated the role of adrenergic components in the pelvic splanchnic nerve on the erectile function in the dog. Electrical stimulation of pelvic splanchnic nerves increased blood flow in the internal pudendal artery and also elevated the cavernous pressure. These increases were blocked in part by phentolamine or methylene blue, but not by propranolol or atropine. The effects of cholinergic and adrenergic agonists and antagonists on mechanical responses were also examined in muscle strips obtained from various arteries in the intrapelvic region including the internal pudendal artery. Norepinephrine induced contraction in the iliac artery and relaxation in the internal pudendal artery, and both the contraction and relaxation responses were blocked by phentolamine but not by propranolol. These findings suggest that in the dog, alpha-adrenergic components projected through the pelvic splanchnic nerve may contribute to penile erection, together with cyclic GMP-mediated mechanisms.     

Reflex limb dilatation following norepinephrine and angiotensin II in conscious dogs.

Effects of intravenous and intra-arterial norepinephrine (NE) and angiotensin II (AN) were compared in 18 conscious dogs instrumented with Doppler or electromagnetic flow probes on the iliac, mesenteric, and renal arteries, and catheters in the aorta and iliac arteries. NE and AN administered intravenously constricted the mesenteric and renal beds, and constricted the iliac bed when administered directly into the iliac artery. In contrast, intravenous NE and AN caused striking reflex increases in iliac flow and reductions in iliac resistance, respectively, in 12 of 18 dogs studied. The reflex iliac dilatation was not prevented by beta blockade with propranolol, cholinergic blockade with atropine, or prostaglandin synthetase inhibition with indomethacin. However, the responses were abolished by either phentolamine, 1 mg/kv iv, or after local blockade of the limb with either phentolamine, 0.5 mg/kg, or with tripelennamine, 2 mg/kg. The dilatation was not prevented by either bilateral carotid sinus and aortic nerve section or by bilateral vagotomy alone, but was prevented by a combination of these procedures. Thus, intravenous NE and AN cause striking reflex iliac dilatation in the limb in the conscious dog; the afferent arc of this reflex involves both arterial baroreceptor and vagal pathways, while the efferent mechanism involves an interaction of alpha-adrenergic and histaminergic receptors.     

Drinking behaviour in the cat induced by renin, angiotensin I, II and isoprenaline.

1. Angiotensin I, II and hog renin, infused into the lateral cerebral ventricles (I.C.V.) of water replete cats, each induced water drinking behaviour. 2. Intravenous infusion of high doses of angiotensin I or II also elicited a drinking response. The dipsogenic effect of I.V. renin was not marked. 3. Drinking in response to I.C.V. angiotensin II was abolished after autonomic ganglion blockade with I.V. hexamethonium or pempidine and was significantly reduced after I.V. atropine methonitrate. 4. The dipsogenic response to I.C.V. angiotensin II was unaffected by either peripheral adrenergic neurone blockade with I.V. bethanidine, alpha-adrenoceptor blockade with phentolamine or beta-adrenoceptor blockade with sotalol. 5. Atropine, atropine methonitrate, hexamethonium and pempidine given I.C.V did not inhibit the diposgenic response to I.C.V. angiotensin II. 6. Bethanidine I.C.V. produced a dose related reduction in the dipsogenic response to I.C.V. angiotensin II. 7. The alpha-adrenoceptor blocking agents tolazoline and phenoxybenzamine given I.C.V did not affect angiotensin induced drinking but the response was regularly inhibited by phentolamine I.C.V. 8. The beta-adrenoceptor blocking agents propranolol and practolol given I.C.V. each inhibited angiotensin induced drinking. The L-isomer of propranolol was a more effective blocker than the D-isomer. 9. Isoprenaline given I.C.V induced drinking in ten of sixteen cats. Subcutaneous administration of isoprenaline also elicited drinking but the onset of the response was delayed and the amount consumed slightly less than after I.C.V infusion.     

Pancreatic polypeptide family (APP,BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to α-adrenoceptor blockade

Electrical stimulation of the cat cervical sympathetic trunk caused submandibular salivary secretion and vasoconstriction simultaneously with a contraction of the nictitating membrane. Following α- and β-adrenoceptor blockade by phentolamine or phenoxybenzamine combined with propranolol, the salivary response and the nictitating membrane contraction upon sympathetic stimulation were almost abolished. A considerable vasoconstrictor response (up to 40% of control) however still remained in the submandibular gland. This yasoconstriction, which persisted after α-adrenoceptor blockade, was rather slow in onset and had a long duration without any poststimulatory hyperemia. Local intra-arterial infusions of noradrenaline caused submandibular vasoconstriction, salivary secretion and nictitating membrane contraction. The blood flow response to exogenous noradrenaline did, however, not mimic the effects of sympathetic nerve stimulation with regard to vascular escape. Whereas the vascular escape after nerve stimulation was followed by a prolonged vasoconstriction with a gradual decline, the escape after noradrenaline infusions was accompanied by a normalization of blood flow. Local intra-arterial infusions of pancreatic polypeptide (PP)-related peptides caused a slowly developing vasoconstriction with a long duration in the submandibular gland, but no salivary secretion or contraction of the nictitating membrane. The relative molar potencies as vasoconstrictory agents were about PYY: 1, neuropeptide Y (NPY): 5, avian and bovine pancreatic polypeptid 100. The vasoconstrictor effects of PP-related peptides were resistant to α-adrenoceptor blockade and present also in sympathectomized animals, suggesting a direct action on vascular smooth muscle. Combined local infusions of noradrenaline and NPY caused a vascular response in the submandibular salivary gland which was similar to that seen upon sympathetic nerve stimulation. PYY and NPY caused increase in systemic arterial blood pressure upon systemic administration which indicates general vasoconstrictor actions. This effect was accompanied by a transient bradycardia which was due to inhibition of sympathetic tone, since it was absent in animals treated with propranolol. In conclusion, the present findings illustrate the differential sensitivity to α-adrenoceptor antagonists of the submandibular vasoconstriction and salivation as well as smooth muscle contraction of the nictitating membrane induced by sympathetic nerve stimulation. This remaining vasoconstriction may be explained by release of a nonadrenergic, PP-related transmitter such as NPY which may be present together with noradrenaline in the vascular nerves. Release of an additional vasoconstrictory factor may also account for the finding that infusions of noradrenaline do not mimic the vascular effects of sympathetic nerve stimulation in vivo.     

Activation of the renin-angiotensin system contributes to the peripheral vasoconstriction reflexly caused by stomach distension in anaesthetized pigs

Gastric distension in anaesthetized pigs reflexly elicits peripheral vasoconstriction and an increase in plasma renin activity (PRA), with vagal afferent and sympathetic efferent limbs. The aim of the present study was to quantify the contribution of the renin-angiotensin system to the peripheral vasoconstriction. In pigs anaesthetized with alpha-chloralose, changes in anterior descending coronary, superior mesenteric and left external iliac blood flow caused by stomach distension before and after blockade of angiotensin II receptors with losartan were assessed using electromagnetic flowmeters. Gastric distension for periods of 30 min was performed by injecting 0.8 l warm Ringer solution into balloons positioned within the viscus. Changes in heart rate and renal blood flow were prevented by atrial pacing and injection of phentolamine into the renal arteries, and changes in regional perfusion pressure and in baroreceptor activity were minimized by aortic constriction and denervation of the carotid sinuses. PRA was assessed by radioimmunoassay of angiotensin I. Before blockade of angiotensin II receptors by administration of losartan, stomach distension decreased coronary blood flow by 14.2 % in six pigs and mesenteric and iliac blood flow by 11 % and 17.3 %, respectively, in another six pigs. After administration of losartan, these decreases were significantly reduced to 7.4 %, 6.8 % and 8.7 %, respectively. The above responses were abolished by bilateral section of the subdiaphragmatic vagal nerves. These results show that the peripheral vasoconstriction reflexly caused by stomach distension was significantly contributed to by the concomitant activation of the renin-angiotensin system.     

Model of cardiovascular injury in magnesium deficiency

Magnesium deficiency is known to produce cardiovascular lesions. It is, however, not clear as to what constitutes magnesium deficiency - reduced serum levels, reduced tissue levels or reduced intracellular levels of the ionic form of the element. This article cites evidence in support of a hypothesis that a fall in serum magnesium levels may trigger a temporal sequence of events involving vasoconstriction, hemodynamic alterations and vascular endothelial injury to produce pro-inflammatory, pro-oxidant and pro-fibrogenic effects, resulting in initial perivascular myocardial fibrosis which, in turn, would cause myocardial damage and replacement fibrosis. Further, angiotensin II may be the prime mover of the pathogenetic cascade in magnesium deficiency. Importantly, such a mechanism of cardiovascular injury would be independent of a reduction in myocardial or vascular tissue levels of magnesium.     

Pharmacological bases of the treatment of cardiac insufficiency

Congestive heart failure is a complex physiopathological state where both myocardial hypo-contraction and excessive peripheral vasoconstriction lead to lower cardiac output. The increase in cytosolic calcium concentration triggers the contractile processus. Digitalis inhibits the Na+/K+ ATPase enzyme and indirectly increases intracellular calcium concentration. beta 1 agonists increase the synthesis of cAMP-dependent protein kinase and hence the recruitment of new receptor-operated calcium channels which increase the calcium influx and the mobilization from its intracellular storage sites. Vascular smooth muscle contraction occurs with calcium influx into the cell resulting from various receptor activation. In congestive heart failure, activation of the sympathetic nervous system and of the renin-angiotensin system leads to neurohumoral-induced peripheral vasoconstriction. Renal effects of angiotensin II and aldosterone are responsible for sodium and water retention. alpha 1-blocking agents are drugs that block competitively the catecholamines effects on vascular receptors. Angiotensin I-converting-enzyme inhibitors block the formation of the key-element of the system: angiotensin II. Both alpha 1-blocking agents and converting-enzyme inhibitors show vasodilatator effects and acutely improve hemodynamic status of patients with congestive heart failure. Converting-enzyme inhibitors exhibit specific improvement of intrarenal hemodynamics and do not induced sodium and water retention in longterm therapy.     

Neuroeffector mechanisms of the defense reaction in the rat

Electrical stimulation of the dorsal periaqueductal gray matter (DPAG) eliciting flight behavior in awake rats caused an increase in arterial blood pressure (BP), heart rate (HR) and respiration in rats anesthetized with urethane. The hypertension was markedly reduced by 5 mg/kg of intravenously injected hexamethonium or bretylium, virtually abolished by 5 mg/kg of phentolamine and partially antagonized by 0.1 mg/kg of the α₁-adrenoceptor blocker, prazosin. The tachycardia induced by DPAG stimulation was partially antagonized by hexamethonium or bretylium and abolished by propranolol (5 mg/kg, IV) or practolol (5 mg/kg, IV), but not affected by N-butylscopolamine (10 mg/kg, IV). Phentolamine increased basal HR and abolished the tachycardic response caused by either brain stimulation or intravenous noradrenaline. Prazosin moderately decreased the response to noradrenaline, but did not affect basal HR or the tachycardia induced by brain stimulation. The increase in respiratory amplitude occurring during brain stimulation was abolished by phentolamine as well as by prazosin, while the increase in respiratory rate was moderately reduced by phentolamine and propranolol. These results demonstrate that the cardiovascular component of the defense reaction of the rat is almost entirely due to a sharp increase in sympathetic tone. They also suggest that the hyperventilation induced by aversive brain stimulation is modulated by central and peripheral adrenergic mechanisms.     

Blockade of pressor responses to angiotensins I and II and noradrenaline using phentolamine,propranolol and hexamethonium in conscious rabbits

Angiotensin I is known to have direct agonist activity at some target tissues, independent of its conversion to angiotensin II. Aspects of its possible direct role as a pressor agent were investigated in conscious rabbits.Phentolamine (3 mg/kg i.v.), a dose which did not affect baseline blood pressure, reduced the pressor response to angiotensin II by 17% (P<0.05) but did not alter the sensitivity to angiotensin I. Noradrenaline activity was reduced by 56%. Propranolol (2 mg/kg i.v.), a dose which did not affect baseline blood pressure but which substantially reduced the depressor response to isoprenaline, had no effect on the pressor activity of either angiotensin I or II. Noradrenaline potency was reduced by 32%. Hexamethonium (20 mg/kg i.v.), caused a potentiation of the response to angiotensin I and II and noradrenaline. This was probably a nonspecific action associated with the decrease in baseline blood pressure. No differential effect of ganglion blockade on the two angiotensins was noted.The dissociation of the effects of phentolamine on angiotensins I and II provides further evidence that pressor actions of these two compounds act through partially different mechanisms.     

Separation of drinking and pressor responses to central angiotensin by monoamines

This study investigated the neurotransmitters involved in the increase in blood pressure and drinking produced when angiotension II is injected intraventricularly (ivt). Using pharmacologic manipulations of the monoamines norepinephrine, dopamine, and serotonin it has been possible to separate the pressor response from dipsogenic responses to angiotension II. Alpha-adrenergic blockade with phentolamine restricted to the brain blocked the pressor response to angiotensin II in a dose-related manner, while drinking remained unaffected. Norepinephrine alone, injected into the ventricles elevated blood pressure, but did not produce drinking. The norepinephrine effect was also blocked by phentolamine by the same ventricular route. Other monoamines were not involved. Dopamine alone did not produce thirst. Cardiovascular effects with dopamine were observed only with large doses. The dopaminergic agonist apomorphine produced no change in blood pressure or drinking. Reduction of central serotonin stores by p-chlorophenylalanine intraperitoneally or 5,7-dihydroxytryptamine intraventricularly had no effect on the pressor or dipsogenic effects of angiotensin II. The serotonin agonist N,N-dimethyl-5-methoxytryptamine ivt did not produce a rise in blood pressure or drinking. It is concluded that the pressor effect of angiotensin II, but not the drinking effect is mediated by noradrenergic stimulation of alpha-receptors. The drinking response does not appear to be mediated by the monoamines.     

Effects of adrenergic blockade on glucose kinetics in septic and burned guinea pigs

We have used the primed-constant infusion of [6-3H]glucose to study the effects of phentolamine, an alpha-adrenergic blocker, and propranolol, a beta-adrenergic blocker, on glucose production and clearance in gastrostomy-fed control, septic (repeated sub-Q Escherichia coli injections), and burned (25-30% BSA) guinea pigs. Hypermetabolism and elevated glucoregulatory hormones were evident in both traumatized models, whereas their glucose kinetic response was different. Basal glucose production and clearance were elevated in the burned group and were depressed in the septic group when compared to control values. Propranolol caused a further increase in glucose production and clearance in the burned group, whereas it depressed glucose production and clearance to an even greater extent in the septic group. Phentolamine also produced an increase in glucose production and clearance in the burned group. In the septic group, phentolamine had no significant effect on glucose production, but clearance was significantly elevated. Thus, although alpha- or beta-adrenergic blockade normalized metabolic rate in both groups with respect to control animals, glucose kinetics remained different despite similar changes in counterregulatory hormones.     

On the role of vasopressin and angiotensin in the development of irreversible haemorrhagic shock

1. Long-lasting haemorrhagic hypotension (4.5 hr at 35 mmHg) leading to irreversible haemorrhagic shock, has been studied in normal dogs, in dogs treated with a bradykinin potentiating nonapeptide (BPP(9a)), which blocks the conversion of angiotensin I to angiotensin II, and in dogs with experimental chronic diabetes insipidus (DI dogs). BPP(9a) was given by I.V. injection before the start of bleeding (BPP pre-treated group), 45 min after blood pressure had reached 35 mmHg (BPP early treated group) or 2 hr after blood pressure had reached 35 mmHg (BPP late-treated group). After retransfusion of blood all dogs were allowed to recover and observed for a further period of 3 days.2. Untreated control dogs developed haemorrhagic shock with tachycardia, low cardiac output, low total peripheral conductance and low stroke volume. All died within 24 hr of retransfusion, with pathological lesions typical of irreversible haemorrhagic shock.3. BPP pre-treated dogs developed haemorrhagic shock with bradycardia (during early shock), high cardiac output, high peripheral vascular conductance and high stroke volume when compared with the untreated controls. All pre-treated animals survived the 3 day observation period. They were then killed and on post-mortem showed no signs of irreversible haemorrhagic shock.4. BPP early-treated animals behaved like controls before BPP, but like pre-treated animals after the drug. Only one out of eight died within the 3 day observation period.5. BPP late-treated dogs behaved like controls before BPP. They responded to the drug with a rise in cardiac output, peripheral vascular conductance and stroke volume, and with a fall in heart rate. These responses were, however, short-lived. Four out of these eight animals died within the 3 day observation period, with lesions of irreversible haemorrhagic shock.6. DI dogs developed haemorrhagic shock with tachycardia (like controls), but with high cardiac output and peripheral vascular conductance (like BPP pre-treated dogs). The stroke volume of DI dogs was intermediate between those of controls and pre-treated groups. All six dogs survived the 3 day observation period.7. BPP(9a) had no measurable effect on the course of endotoxic shock.8. It is suggested that the normally severe vasoconstriction of the mesenteric vascular bed, which is thought to be responsible for irreversible haemorrhagic shock, is absent or attenuated in the absence of vasopressin or angiotensin. The consequences of this on the development of irreversibility are discussed.     

Angiotensin and the hemodynamics of chronic salt deprivation.

Salt deprivation has been shown to cause fluid volume contraction and marked renin release; it is not clear whether angiotensin-induced vasoconstriction adds to low volume in compromising circulatory function or whether there are additional facets to the salt-deprived state. Mature Wistar rats were fed a low-salt diet for 1 mo and then, under pentobarbital anesthesia, compared to normals. Arterial pressure (is congruent to 125 mmHg), cardiac output (is congruent to 200 ml/min per kg), and total peripheral resistance were nearly identical in both groups. The influence of angiotensin was estimated by injecting converting enzyme inhibitor (SQ 20881, 1 mg/kg), and then observing the immediate hemodynamic response. Salt-deprived rats responded with a large (-47 mmHg) fall in pressure and total peripheral resistance indicating that, although total peripheral resistance was normal in salt deprivation, an increased fraction (30% vs. 11%) of the resistance was supported by angiotensin. Cardiac output decreased (-8%) in contrast to the increase that would be expected during marked arterial dilation; elevated angiotensin levels may have caused a moderate, beneficial decrease in venous compliance. These results suggest that circulatory function is adequately maintained during salt deprivation by a combination of normal total peripheral resistance and decreased venous compliance.     

Atropine-sensitive, tetrodotoxin-resistant contraction induced by noradrenaline in isolated cat rectum

Effects of noradrenaline (NA) on the isolated rectal circular muscle of the cats were studied in comparison with the effects on the internal anal sphincter (IAS). NA (10(-8)-10(-7) g/ml) caused tonic contraction in four of 15 strips of the rectum taken from 15 animals, and in all 15 strips of the IAS. Phenylephrine also induced rectal and IAS contraction. Rectal contraction induced by NA was resistant to phentolamine, yohimbine, propranolol, hexamethonium and tetrodotoxin, but blocked by atropine. IAS contraction induced by NA was resistant to propranolol, atropine, hexamethonium and tetrodotoxin, but blocked by phentolamine and yohimbine. It is suggested that an atropine-sensitive excitatory adrenergic mechanism other than the excitatory alpha-adrenergic mechanism exists in the rectal circular muscle.     

Role of alpha 1-adrenoceptors in norepinephrine-induced cardiomyopathy.

This study practically delineated the contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine (NE) cardiomyopathy. A total of 64 adult New Zealand white rabbits were used. NE cardiomyopathy was produced in rabbits by a 90-minute intravenous infusion of norepinephrine (2 micrograms/kg/min at infusion rate 0.382 ml/min). Arterial blood pressure and heart rate were constantly monitored. Arterial blood samples were obtained at 30-minute intervals for measurements of pH, blood gases, and glucose. Alpha-adrenoceptor blocking agents, when employed, were given 15 minutes prior to the initiation of NE infusion. Two days after treatment the rabbits were killed. The hearts were examined microscopically and assigned a histologic score. Pretreatment with the alpha 1-adrenoceptor blocker prazosin at 50, 100, or 200 micrograms/kg significantly reduced NE-induced myocardial injury in a dose-related manner. In contrast, the presence of alpha 2-adrenoceptor blocker yohimbine at 2.5 or 5.0 mg/kg was ineffective in preventing the formation of myocardial lesions. These findings suggest that NE cardiomyopathy may result largely from activation of the alpha 1-adrenoceptor system in the rabbit model.     

alpha- and beta-Adrenergic effects of epinephrine on ventricular pacemakers in dogs

We studied the effects of epinephrine on idioventricular rhythm in 15 adult dogs with chronic complete heart block induced by the injection of formalin into the His bundle. Atropine (0.1 mg/kg) was given intravenously to attenuate any potential vagal effects, and epinephrine was infused in graded doses of 0.01-10.0 micrograms.kg-1.min-1. Two different responses were seen. In 12 dogs there was a concentration-dependent increase in ventricular rate following epinephrine infusion. These animals then were given the beta-blocker propranolol (0.5 mg/kg iv), and the epinephrine infusions were repeated. In this situation epinephrine concentrations less than 0.1 micrograms.kg-1.min-1 induced a decrease in ventricular rate with no associated change in arterial pressure. In four additional dogs this decrease in ventricular rate was prevented by alpha-blockade with phentolamine. In three dogs epinephrine less than 0.1 micrograms.kg-1.min-1 induced a decrease in ventricular rate without an associated change in arterial blood pressure. This decrease in rate was abolished by the alpha-blocker phentolamine. It therefore appears that an alpha-adrenergic effect on ventricular automaticity can occur in the intact animals. When this does not occur initially, it can be unmasked by propranolol and results in a slowing of ventricular rate unrelated to changes in blood pressure.     

Carotid artery constriction in acute hypertension.

The effects of carotid artery constriction on cerebrovascular ultrastructure and permeability in acute hypertension have been assessed. The right common carotid artery of 26 male Wistar-Kyoto normotensive rats was constricted with a silver wire clip. Forty-eight hours later these animals received an angiotensin amide injection (1 microgram/kg body weight) or infusion for 3--4 hours (0.5 or 1.7 microgram/min/kg body weight) or were subjected to subdiaphragmatic aortic constriction. All animals were injected with horseradish peroxidase (HRP) (20 mg/100 g body weight) and sacrificed after 5--15 minutes. Parietal cortex from both hemispheres was processed for light and electron-microscopic examination. The arterial vessels of the right hemisphere from animals given injections of or infused with angiotensin II exhibited increased permeability to HRP, as manifested by the presence of reaction product in interendothelial cell clefts, in subendothelial space, in endothelial and smooth muscle cell pinocytotic vesicles, and along smooth muscle cell basal laminas. In contrast, no alterations in the permeability of ipsilateral vessels were seen in rats with aortic constriction. Cerebral cortical arterial vessels from the left hemisphere in all groups of animals exhibited segmental dilatation and constriction and abnormal permeability to HRP. The results suggest that angiotensin administration can produce increased permeability of cerebral cortical vessels in the absence of elevated blood pressure.     

Hypotension and thirst in rats after phentolamine treatment

Administration of the α-adrenergic receptor blocker phentolamine is known to lower arterial blood pressure and to increase renin secretion and water intake in rats. In the present experiments, drinking by rats after subcutaneous administration of the drug was found to be inversely related to arterial blood pressure within the range of 60–90 mm Hg. Drug treatment in nephrectomized rats led to such severe hypotension that drinking was precluded. Pretreatment with propranolol moderated the hypotension in nephrectomized rats and drinking was not attenuated. These results parallel those of previous experiments using the β-adrenergic receptor agonist isoproterenol. Collectively, they suggest that after treatment with these hypotensive agents, a stimulus for thirst can arise from some factor other than angiotensin. This stimulus, perhaps mediated by arterial baroreceptors, is additive in its effects on thirst with the stimulus induced by hypertonic NaCl or subcutaneous colloid treatments.