Central adrenomedullin augments the baroreceptor reflex in conscious rabbits

We examined the roles of central adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP), and calcitonin gene-related peptide (CGRP) on the baroreceptor reflex in conscious rabbits. Intracerebroventricular injection of adrenomedullin (0.2 and 1 nmol/80 microL) elicited dose-related increases in arterial pressure and renal sympathetic nerve activity. On the other hand, a subpressor dose of intracerebroventricular infusion of adrenomedullin (1 nmol/300 microL per hour) caused significant increases in baroreflex sensitivities assessed by renal sympathetic nerve activity and heart rate compared with vehicle infusion (Gmax; -14.9+/-1.7 versus -8.0+/-0.7%/mm Hg, P<0.01, and -8.1+/-0.8 versus -5.1+/-0.5 bpm/mm Hg, P<0.01, respectively). Intracerebroventricular infusion of CGRP (1 nmol/300 microL per hour), which is structurally homologous to adrenomedullin, also enhanced the baroreflex controls of renal sympathetic nerve activity and heart rate. However, the intracerebroventricular infusion of PAMP (30 nmol/300 microL per hour) failed to alter the baseline levels of arterial pressure and baroreflex sensitivities. These results suggest that central adrenomedullin and CGRP, but not PAMP, participate in cardiovascular regulation to augment the baroreflex controls of renal sympathetic nerve activity and heart rate in conscious rabbits.     

Enhanced responsiveness to carotid baroreceptor unloading in conscious dogs during development of perinephritic hypertension

The effects of unloading the carotid sinus baroreceptors before and during the development of perinephritic hypertension were studied in conscious dogs instrumented with aortic catheters to measure arterial pressure and heart rate, and electromagnetic flow probes to measure cardiac output and calculate total peripheral resistance. Prior to hypertension, bilateral carotid occlusion (BCO) increased mean arterial pressure by 38 +/- 2 from 101 +/- 2 mm Hg and total peripheral resistance by 19 +/- 2 from 46 +/- 3 mm Hg/l/min, while cardiac output and heart rate did not change from 2,299 +/- 128 ml/min and 84 +/- 4 beats/min, respectively. At 2 weeks after renal wrapping, there were significant increases in baseline mean arterial pressure, cardiac output, and total peripheral resistance and decreases in heart rate; BCO increased mean arterial pressure by 59 +/- 5 from 130 +/- 4 mm Hg, heart rate by 36 +/- 5 beats/min from 69 +/- 3 beats/min, and cardiac output by 458 +/- 103 from 2,711 +/- 239 ml/min. By 4 weeks after renal wrapping, heart rate and mean arterial pressure responses to BCO were approaching baseline levels. After beta-adrenergic receptor blockade, responses to BCO of mean arterial pressure, cardiac output, and heart rate were no longer significantly enhanced during the development of hypertension. Thus, in conscious dogs, reflex pressor responses to baroreceptor unloading via BCO were enhanced during the development of hypertension but no longer present 3 weeks later. The augmented mean arterial pressor responses to BCO were mediated by increases in cardiac output and heart rate, which in turn, appeared to be controlled by beta-adrenergic receptor mechanisms.     

Impaired arterial baroreceptor reflex and cardiopulmonary vagal reflex in conscious spontaneously hypertensive rats

The activity of baroreceptor reflexes and cardiopulmonary reflexes was examined in conscious spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats. The baroreceptor heart rate reflex, elicited by phenylephrine- and nitroprusside-induced changes in blood pressure, had a reduced range and lower heart rate plateau in SHR than in WKY rats, which suggests impaired vagal control of the heart rate in SHR. Cardiopulmonary receptor reflex activity was assessed by intravenous injections of phenyldiguanide which evoke the Bezold-Jarisch reflex. Phenyldiguanide elicited dose-dependent bradycardic and hypotensive responses in WKY rats, but these were significantly attenuated in SHR. This is the first demonstration of impaired Bezold-Jarisch responses in conscious SHR and provides evidence of both impaired vagally mediated arterial baroreceptor activity and impaired cardiopulmonary receptor activity in this rat strain.     

Angiotensin-converting enzyme inhibitor resets baroreceptor reflexes in conscious dogs

The present experiments investigate whether the absence of tachycardia during lowering of blood pressure (BP) with an angiotensin-converting enzyme inhibitor (CEI) in salt-depleted dogs is due to an alteration in the activity of the baroreflex. Baroreflex activity was measured after pharmacological manipulation of BP using intravenous nitroglycerin or phenylephrine, and the heart period (R-R interval) relative to the arterial pressure pulse was recorded. The slope of the relationship between BP and R-R interval is a measure of the sensitivity of the baroreceptor reflex and displacement of the line indicates a change in the setpoint of BP. On normal sodium diet, the sensitivity and setpoint of the baroreflex were unaltered by the nonapeptide CEI given both intravenously and into a lateral cerebral ventricle. During salt depletion. however, intravenously but not centrally administered CEI altered the setpoint of the baroreflex without modifying the sensitivity. The alteration in the setpoint that occurred following intravenous CEI in the salt-depleted dog could well account for the fact that the fall in BP induced by CEI does not cause reflex tachycardia. These results indicate that circulating but not brain angiotensin II is essential for the maintenance of baroreflex function during sodium depletion and provide further evidence for the important interactions between angiotensin and the autonomic nervous system.     

Interaction between angiotensin II and the baroreceptor reflex in the control of adrenocorticotropic hormone secretion and heart rate in conscious dogs

The present studies were designed to examine the effect of angiotensin II on baroreflex control of adrenocorticotropic hormone secretion and heart rate in conscious dogs. Baroreflex function was assessed by examining the relationship between blood pressure and plasma corticosteroid concentration (used as an index of adrenocorticotropic hormone secretion) and between blood pressure and pulse interval (the inverse of heart rate). Blood pressure was varied by intravenous infusion of four doses (0.3, 0.6, 1.5, and 3.0 micrograms/kg per min) of the vasodilator nitroprusside. Nitroprusside infusion produced an increase in plasma corticosteroid concentration and a decrease in pulse interval, both of which were linearly related to the fall in arterial blood pressure. During infusion of angiotensin II (10 ng/kg per min), however, the lines relating blood pressure to plasma corticosteroid concentration or blood pressure to pulse interval were shifted to a higher pressure level, suggesting that angiotensin II resets the baroreceptor reflex. Angiotensin II blockade with saralasin, an angiotensin II antagonist, or with captopril, a converting enzyme inhibitor, in sodium-depleted dogs with elevated plasma angiotensin II levels produced a shift in the opposite direction in these relationships. Because baroreflex function in sodium-depleted dogs before angiotensin II blockade was similar to that in sodium-replete dogs, despite the increased plasma angiotensin II levels, and because treatment of sodium-replete dogs with saralasin did not affect baroreflex function, these results suggest that endogenous angiotensin II is necessary for the maintenance of normal baroreflex control of adrenocorticotropic hormone secretion and heart rate during sodium depletion. Previous studies designed to evaluate the physiological significance of angiotensin II in the control of adrenocorticotropic hormone secretion showed that high, perhaps supraphysiological, levels of exogenous angiotensin II are required to increase adrenocorticotropic hormone secretion. An additional finding of the present study was that exogenous angiotensin II produces a larger increase in adrenocorticotropic hormone secretion when the pressor effect of angiotensin II was eliminated with simultaneous infusion of the vasodilators nitroprusside or hydralazine. This result suggests that experiments that evaluate the physiological role of angiotensin II in the control of adrenocorticotropic hormone secretion with infusions of exogenous AII may underestimate the importance of endogenously produced angiotensin II, which is normally released without an increase in pressure.     

Carotid sinus baroreceptor reflex in dogs with experimental heart failure

We have previously demonstrated a decrease in baroreceptor discharge sensitivity in dogs with experimental heart failure. In the present study, we determined the sensitivity of the carotid sinus baroreceptor reflex in dogs with pacing-induced heart failure. The carotid sinus baroreceptor reflex sensitivity was determined by pressurizing one carotid sinus with all other baroreceptor and cardiopulmonary receptor inputs removed. The data were analyzed by plotting carotid sinus pressure-mean arterial pressure curves and carotid sinus pressure-renal sympathetic nerve activity curves in the two groups of dogs. The peak arterial pressure during carotid hypotension was significantly depressed in dogs with heart failure compared with normal dogs (107.1 +/- 5.7 versus 139.8 +/- 7.0 mm Hg, p less than 0.001). Mean arterial pressure range, renal sympathetic nerve activity range, and peak slope were significantly decreased in the heart-failure group. To determine if this depression was completely due to depression of baroreceptor discharge per se, or to alterations in central or end-organ responsiveness, similar experiments were performed by stimulating the carotid sinus nerve and evaluating frequency, voltage, and duration of stimulation on the resultant mean arterial pressure and renal sympathetic nerve activity. As was the case with carotid sinus pressurization, electrical stimulation caused a significantly smaller change in mean arterial pressure in heart-failure dogs compared with the normal dogs. However, there was no significant difference between normal and heart-failure dogs for the renal sympathetic nerve activity-electrical stimulation curves. These data strongly suggest that the depressed carotid sinus baroreceptor reflex in heart failure is not solely the result of depressed baroreceptor responsiveness but may be related to poor end-organ responses and normal central control of renal sympathetic outflow.     

Carotid sinus and cardiopulmonary baroreceptor reflex in patients with hypertension]

The nature of sinocarotid and cardiopulmonary baroreceptor reflex was examined in 33 patients with labile hypertensive disease (HD). The mechanic receptors of the sinocarotid area was activated by a neck barochamber; lower extremity decompression was used to test the vasoconstrictor cardiopulmonary baroreflex. The studies demonstrated that the activation of the mechanic receptors led to less severe bradycardia in hypertensives than in healthy persons. At the same time blood pressure fall with a decrease in neck chamber pressure achieved higher values in the patients than in normotensives, which was due to vasodilation in most patients. A direct relation was proved to exist between the degree of a decrease in the cardiochronotropic baroreflex component, presence of its vasomotor component, and disease duration. The hypertensives displayed increased in vasoconstrictor cardiopulmonary baroreceptor reflex.     

Effect of angiotensin II on baroreceptor reflex control of heart rate in conscious baboons

Studies of the baroreceptor-heart rate reflex were performed in four conscious, unrestrained male baboons to determine whether changes in circulating angiotensin II within the physiological range are associated with alterations in baroreceptor reflex sensitivity. With the animals on a high sodium intake, studies were performed before and during graded angiotensin II infusion (10 and 20 ng/kg/min). To separate effects on baroreceptor reflex function mediated by angiotensin II-induced increases in arterial pressure, these studies were repeated on a different day with simultaneous glyceryl trinitrate infusion to prevent increases in pressure during angiotensin II infusion. With the animals on a low sodium intake, studies were performed before and after angiotensin converting enzyme inhibition with captopril (1 and 5 mg/kg). These studies were also repeated on a separate day during simultaneous phenylephrine infusion to prevent a decrease in pressure with captopril. Reduction in sodium intake had no significant effect on arterial pressure, heart rate, or plasma volume, although arterial plasma angiotensin II concentration and renin activity were significantly increased (p less than 0.01). Infusion of angiotensin II produced a significant reduction in baroreceptor reflex sensitivity (p less than 0.01), and converting enzyme inhibition produced a significant increase (p less than 0.05). These effects accompanied significant increases and decreases in arterial angiotensin II concentration, respectively (p less than 0.01), but were independent of angiotensin II-related changes in arterial pressure. The data indicate that physiological variations in circulating angiotensin II have a direct effect on sensitivity of the baroreceptor-heart rate reflex.     

Effects of gender and age on the cardiac baroreceptor reflex in hypertension.

The present study examined whether alterations in the cardiac baroreceptor reflex in hypertension may be a function of constitutional differences associated with gender and age. These hypotheses were tested using a cross-sectional design that compared 20 normotensive and 21 hypertensive men and women of varying age for differences in baroreceptor reflex sensitivity and response latency for heart rate, obtained using a modified bolus phenylephrine (Oxford) method. Relative to their respective normotensive controls, baroreceptor reflex sensitivity was reduced in hypertensive men, but not in hypertensive women. Among normotensive subjects, men had greater baroreceptor reflex sensitivity than women. Independent from the effects associated with differences in blood pressure, age was not a significant predictor of reduction in baroreceptor reflex sensitivity. However, a combination of high blood pressure and older age was associated with a significant increase in baroreceptor reflex response time. In summary, gender and aging interacted with hypertension to alter two different aspects of the baroreceptor reflex. These results provide a preliminary indication that a decline in arterial baroreflex sensitivity may be more specific to hypertension in men than in women. Prolongation in baroreflex response latency in older hypertensive subjects also suggested that aging and hypertension may have a synergistic effect on cardiac parasympathetic function.     

The baroreceptor reflex as a predictor of crises in arterial hypertension]

The sensitivity of baroreceptor reflex was determined by the "neck chamber" method at a pressure of 40 mm Hg in patients with mild, moderate and malignant arterial hypertension (AH). A 24-hour blood monitoring was performed in patients with mild and moderate AH. There was a negative correlation between the lowering values in blood pressure on baroreceptor stimulation and the incidence of hypertensive crises in all the groups. There was also a negative correlation between the baroreceptor sensitivity and the daily blood pressure variations in patients with moderate AH. The findings suggest that a decrease in baroreceptor sensitivity might be a predictor of the critical course of AH.     

Effects of baroreceptor denervation on volume loading hypertension in anephric dogs

The role of the baroreceptor mechanism in determining the relationship between fluid volume and arterial pressure is not clear. Therefore, the effects of the baroreflex on the arterial pressure and fluid volume of conscious, anephric dogs were studied after a sustained 10% increase in blood volume. The animals were equipped with long-term indwelling arterial and venous catheters, and arterial pressure was monitored 24 hours a day. The increase in blood volume was achieved by intravenous infusion of 50 ml/kg of lactated Ringer's solution in 30 minutes. After volume loading arterial pressure increased rapidly to hypertensive levels (130.8 +/- 7.5% of control) in a baroreceptor denervated group. The initial increase in arterial pressure in a group of normally innervated dogs was smaller (118.8 +/- 1.8% of control), but by 24 hours postinfusion the arterial pressure of both groups had reached the same level. The innervated group had probably experienced baroreceptor resetting by this time. Blood volume both before and after infusion was not different in the denervated and innervated groups; however, sodium space was markedly higher before the infusion in the denervated dogs (431.8 +/- 13.8 ml/kg vs 344.8 +/- 19.0 ml/kg in the innervated dogs), and the volume load caused parallel increases in this space in the denervated and innervated groups. The present study shows that the blood volume of anephric dogs was unchanged after baroreceptor denervation while the extracellular fluid volume of denervated dogs was elevated. Furthermore, a small sustained increase in blood volume in either conscious, innervated dogs or conscious, baroreceptor denervated dogs, in contradistinction to the effects in anesthetized dogs, resulted in significant increases in arterial pressure (p less than 0.05).     

Intraileal capsaicin inhibits gastrointestinal contractions via a neural reflex in conscious dogs

BACKGROUND & AIMS: The aim of the present study was to determine the effect of intraileal administration of capsaicin on gastrointestinal motility. METHODS: Mongrel dogs equipped with strain gauge force transducers on the stomach, small intestine, and colon were used. We studied the effects of intraileal capsaicin on gastrointestinal contractions with or without pharmacologic antagonists. The effects of capsaicin administration into the lumen of innervated and extrinsically denervated ileal Thiry loops were also studied. RESULTS: Intraileal capsaicin dose dependently inhibited postprandial contractions at all sites and interdigestive contractions in the upper gastrointestinal tract. Intraileal capsaicin-induced inhibition of gastrointestinal contractions was partially reversed by a nitric oxide (NO) synthase inhibitor, a 5 hydroxytryptamine-3 receptor antagonist (5-HT(3)), and an opiate antagonist. Administration of capsaicin into the innervated ileal Thiry loop had inhibitory effects on gastrointestinal contractions, but gastrointesinal motor activity was not affected by capsaicin administered into the extrinsically denervated Thiry loop. CONCLUSIONS: Stimulation of ileal afferent fibers by capsaicin inhibits gastrointestinal contractions via an extrinsic neural reflex.     

Development of hypertension from unilateral renal artery stenosis in conscious dogs

The renal and systemic changes after stenosis of the left renal artery (n = 5) or sham stenosis (n = 6) in conscious dogs were studied sequentially over 25 days. Stenosis produced a prompt rise in arterial pressure, which was at all times due to reduced peripheral vascular conductance, with no increase in cardiac output despite initial evidence of mild fluid retention. The decrease in peripheral conductance was attributable to 1) the stenotic kidney (25% of the total and due to the mechanical effect of the stenosis itself), 2) the nonstenotic kidney (about 15% of the total and not caused by angiotensin II), and 3) the nonrenal vasculature (60%). The decrease in conductance in the nonrenal vasculature was due partly to angiotensin II, but there was also a gradually developing non-angiotensin II component. Acute administration of captopril caused significantly greater changes in arterial pressure and peripheral conductance throughout the period of stenosis than before stenosis (and greater than in sham-stenosis dogs), indicating that angiotensin II was constricting the peripheral vasculature even when plasma renin levels were no longer elevated. In the stenotic kidneys, captopril produced a fall in renal vascular resistance, but renal blood flow did not rise because there was an approximately equal rise in the resistance of the stenosis. There was no evidence for a role for the autonomic nervous system in the hypertension, as ganglion blockade (pentolinium) had similar hemodynamic effects before and after stenosis. Thus, the hypertension was due at all times to reduced peripheral conductance, with the two kidneys responsible for 40% of this reduced conductance.     

Serotonin blockade in conscious, unrestrained cirrhotic dogs with portal hypertension

It has recently been reported that the administration of ketanserin, a serotonin antagonist, was associated with a significant reduction in portal pressure both in portal hypertensive rats and cirrhotic patients. However, this beneficial effect on splanchnic hemodynamics was accompanied by a significant reduction in arterial pressure. Using conscious dogs, we investigated the effect of the chronic oral administration of a new specific antiserotonergic drug, ritanserin (10 mg per day for 5 days), on portal pressure and systemic hemodynamics. Eleven dogs with secondary biliary cirrhosis and portal hypertension due to chronic bile duct ligation were evaluated. One week prior to study, heparinized catheters were placed in the portal vein and brought subcutaneously to the dorsal cervical area. Measurements were made under baseline conditions, following ritanserin administration and 72 hr after the last dose. Ritanserin administration caused a significant reduction in portal pressure (from 17.3 +/- 3.1 mmHg to 13.6 +/- 4.5 mmHg; mean decrease: 23.1%; p less than 0.001). Maximal effects on portal pressure were reached on the fourth day. During the recovery period, hemodynamic parameters returned to baseline values. In six of the 11 cirrhotic dogs with successful chronic catheterization of the inferior vena cava and aorta, ritanserin administration did not cause significant changes in the mean arterial pressure, heart rate, cardiac output and peripheral vascular resistance. These data indicate that chronic implantation of venous and arterial catheters in dogs with secondary biliary cirrhosis is a useful experimental model for pharmacological studies of portal hypertension in conscious animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in diastolic cardiac function in developing and stable perinephritic hypertension in conscious dogs

The effects of developing perinephritic hypertension (2-3 weeks) and a more stable period of perinephritic hypertension (approximately 14 weeks) were examined on indexes of left ventricular (LV) diastolic function in conscious, chronically instrumented dogs. The complete period of diastole was studied using indexes of isovolumic relaxation (tau), early filling (LV +dD/dt), and stiffness (myocardial stiffness and chamber stress/diameter ratio). During developing hypertension, increased LV end-diastolic pressure, LV end-diastolic stress, peak filling rate, myocardial stiffness, and the stress/diameter ratio increased (p less than 0.05); the time constant tau was not changed. These changes were associated with preserved baseline levels of coronary blood flow (radioactive microspheres) but an impaired coronary vasodilator response to adenosine. Acute administration of phenylephrine in the normotensive dogs caused increases in systolic and diastolic stress and resulted in increases in myocardial stiffness and in the stress/diameter ratio similar to values observed in developing hypertension. During stable hypertension, LV end-diastolic stress, peak filling rate, and both parameters of late-diastolic function (myocardial stiffness and stress/diameter ratio) returned toward control values, but the isovolumic relaxation time constant was increased. Quantitative histological evaluation revealed no increase in stainable connective tissue in dogs with stable hypertension compared with control dogs, and hydroxyproline concentration was not increased in the subendomyocardium, midmyocardium, or subepimyocardium of the dogs with chronic perinephritic hypertension. Thus, in developing hypertension, major alterations in diastolic function were observed that were not structurally related, since these changes 1) could be induced in normal dogs by increasing preload and afterload acutely with phenylephrine and 2) were improved during the ensuing stable period of hypertension.     

Carotid baroreceptor reflex coronary vasodilation in the dog

The hypothesis that neurally mediated coronary vasodilation occurs as part of the carotid baroreceptor reflex was investigated. The left main coronary artery was cannulated and perfused at constant pressure (100 mm Hg) in closed-chest, chloralose-anesthetized dogs. The heart was paced at a constant rate between 60 and 70 beats/min after atrioventricular heart block. Propranolol (1 mg/kg) was given to prevent beta-receptor-mediated alterations in contractility. Aortic blood pressure was stabilized with a blood reservoir. The aortic depressor nerves were cut bilaterally to prevent the buffering influence of aortic arch baroreceptors on the carotid baroreceptor reflex. The carotid sinuses were vascularly isolated and perfused with arterial blood at controlled pressures. Under these conditions, a step change in carotid sinus pressure from 70 to 210 mm Hg produced a 0.29 ml/min per g increase in coronary flow above control and a 10 mm Hg increase in coronary sinus blood oxygen tension. A step in carotid sinus pressure from 70 to 150 mm Hg resulted in a flow increase of 0.13 ml/min per g and a coronary sinus oxygen tension increase of 5.3 mm Hg relative to prestimulation values. Atropine (0.5 mg/kg, iv) blocked most of the reflex coronary vasodilation, indicating a parasympathetic component, and the addition of adrenergic alpha-receptor blockade with phenoxybenzamine (0.25 mg/kg, ic) abolished the remaining response, demonstrating sympathetic participation. The reflex nature of the coronary response was confirmed with carotid sinus denervation and vagotomy. It is concluded that carotid sinus hypertension results in a graded reflex neural coronary vasodilation independent of myocardial metabolic factors. The major component is due to activation of parasympathetic coronary vasodilator fibers, but there is also inhibition of sympathetic vasoconstrictor fibers.     

Alpha-adrenergic-mediated reduction in coronary blood flow secondary to carotid chemoreceptor reflex activation in conscious dogs

We examined the late coronary vascular response to carotid chemoreceptor reflex activation in normal, conscious dogs instrumented for the measurement of right main and left circumflex coronary artery blood flows, arterial and right ventricular pressures, and arterial and coronary sinus blood gases and O2 contents. With heart rate held constant by electrical stimulation, and with respiration controlled or allowed to vary spontaneously, carotid chemoreceptor reflex activation (induced by intracarotid nicotine) elicited a striking biphasic coronary vascular response characterized by an early dilation (previously described) and a late constriction. For example, with respiration controlled and with the autonomic nervous system intact, carotid chemoreceptor reflex activation resulted in a late increase in arterial pressure (19 +/- 4%; P less than 0.002), absolute reductions in right main (24 +/- 4%; P less than 0.002), and left circumflex (12 +/- 2%; P less than 0.004) coronary blood flows, and increases in right (62 +/- 13%; P less than 0.002) and left (26 +/- 3%; P less than 0.0001) coronary resistances. This carotid chemoreceptor reflex activation-induced late coronary constriction was also associated with a concomitant increase in myocardial oxygen extraction, i.e., arterial oxygen content remained constant, while coronary sinus oxygen content decreased (19 +/- 6%; P less than 0.04). Neither propranolol nor atropine had any significant effect on the magnitude of the right coronary constriction. However, both the absolute reduction in right coronary blood flow and increase in right coronary resistance were abolished by phentolamine. Furthermore, either total cardiac denervation or adrenalectomy significantly attenuated (P less than 0.01) carotid chemoreceptor reflex activation-induced reductions in right coronary blood flow and increase in right coronary resistance. We conclude that, with autonomic nervous system activity intact, carotid chemoreceptor reflex activation can elicit an absolute reflexly mediated reduction in coronary blood flow in the normal, conscious dog, despite an increase in arterial pressure. The mechanism of this vasoconstriction involves alpha-adrenergic receptor stimulation mediated by both cardiac sympathetic nerves and circulating catecholamines.     

Angiotensin-induced hypertension in the rat. Sympathetic nerve activity and prostaglandins

To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE2, prostacyclin derivative 6kPGF1 alpha, and thromboxane [Tx] derivative TxB2). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE2 did not increase in angiotensin rats; however, both 6kPGF1 alpha and TxB2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 micrograms/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF1 alpha or TxB2. Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG.