Reactivity of the hypothalamo-pituitary-adrenocortical system in rats with hereditary arterial hypertension

The function of hypothalamo-hypophyseal-adrenocortical system was studied in rats with inherited stress-sensitive arterial hypertension (ISSAH). The rats have been bred from the outbred Wistar strain. It was found that plasma corticosteroid level in ISSAH rats was lower after immobilization stress and higher after stress induced by a combination of stress-factors (ether, 0.7 ml blood loss, novel situation), as compared to Wistar rats. ISSAH rats also showed a reduced reaction to intracerebroventricular noradrenaline (10 micrograms) injection. It was concluded that the changes of noradrenergig brain mechanisms can be responsible for the alterations in the central regulation of blood pressure and adrenocortical function in ISSAH rats.     

Respiratory effects of pressor and depressor agents in conscious rats

We hypothesized that the respiratory baroreflex in conscious rats is either more transient, or has a higher pressure threshold than in other species. To characterize the effect of arterial pressure changes on respiration in conscious rats, ventilation (V) was measured by the plethysmographic technique during injections, or infusions, of pressor and depressor agents. Bolus injections of angiotensin II (Ang II) or arginine vasopressin (AVP), transiently increased mean arterial pressure (MAP; mean +/- SE) 43+/-6 and 28+/-5 mm Hg (1 mm Hg = 133.3 Pa), respectively, and immediately reduced tidal volume (Vt) and, in the case of AVP, V. In contrast, by 10 min of a sustained elevation of MAP (40+/-3 mm Hg) with infusion of Ang II, Vt, f, and V were not different from control levels. Bolus injection of sodium nitroprusside (SNP) to lower MAP (-28+/-3 mm Hg) immediately increased breathing frequency (f) and V, whereas sustained infusion of SNP to lower MAP (-21+/-3 mm Hg) did not change for V at 10 and 20 min. In conscious rats, both injection and infusion of the pressor agent PE (+40 to 50 mm Hg) stimulated f and V; this contrasted with anesthetized rats where PE inhibited f and V, as reported by others. In conscious rats, respiratory responses associated with baroreflexes adapt rapidly and, in the case of PE, can be overridden by some other mechanism.     

Cardiovascular effects of delta 9- and delta 9(11)-tetrahydrocannabinol and their interaction with epinephrine

The administration of delta-9-tetrahydrocannabinol (delta 9-THC, 0.078-5.0 mg/kg, i.v.) to rats anesthetized with pentobarbital caused as much as a 50% decrease in mean arterial blood pressure, heart rate and respiratory rate in a dose-dependent manner. Delta-9(11)-tetrahydrocannabinol (delta 9(11)-THC) was approximately 8-fold less potent than delta 9-THC in its hypotensive effect and had smaller effects on heart and respiratory rates that were not dose-related at doses below 5 mg/kg. Alternate injections of epinephrine (2 micrograms/kg) with vehicle and increasing cannabinoid doses (1.25-5.0 mg/kg) indicated a potentiation of both the duration of the pressor effect and the magnitude of the reflex bradycardic effect of epinephrine by both delta 9- and delta 9(11)-THC. Epinephrine also produced arrhythmias in rats receiving cannabinoids, but not in rats receiving alternate injections of vehicle. It is concluded that both cannabinoids have adverse effects on the cardiovascular system and adverse interactions with epinephrine in rats anesthetized with pentobarbital.     

Changes of mean arterial pressure of the rat resulting from intracerebroventricular injections of prostacyclin or 6-keto-prostaglandin F1 alpha

Repeated intracerebroventricular injections of 1 microgram prostacyclin reduce mean arterial pressure of conscious normotensive rats and reverse the elevation of blood pressure of conscious rats resulting from the intraventricular injection of angiotensin II. The reduction of blood pressure of normotensive rats by prostacyclin is enhanced by pretreatment with probenecid, an inhibitor of fatty-acid transport across biological membranes. Although probenecid does not completely inhibit the transport of fatty acids from the brain to the periphery, the greater effectiveness of prostacyclin in probenecid-treated animals suggests that centrally injected prostacyclin need not leak into the periphery to reduce blood pressure. When the dose of prostacyclin is reduced to 100 ng repeated each minute for 10 min, no change of blood pressure of normotensive rats is observed. The failure of the lower dose of prostacyclin to reduce blood pressure may be due to its rapid degradation. Ventricular injections of 6-keto-prostaglandin F1a, a major product of prostacyclin metabolism, causes an increase of blood pressure which may counteract the action of prostacyclin itself.     

Noradrenaline synthesis during the first week of life and development of inherited stress-induced arterial hypertension in rats

Increasing of the noradrenaline synthesis with daily i.p. administration of synthetic noradrenaline precursor DL-Threo on the 21-25th day of life of the rats with inherited stress-induced arterial hypertension (ISIAH) resulted in a drop of basal and stress-induced blood pressure in adult animals with no changes in response of the hypothalamic-pituitary-adrenocortical system (HPAS). Reduction of the noradrenaline synthesis with daily i.p. administration of dopamine-hydroxylase inhibitor FLA-57 in 21-25th day old Wistar rats induced no arterial hypertension in adults but decreased their adrenocortical response to emotional stress. Noradrenaline deficit in the brain structures on the 4th week of life in rats seems to be associated with arterial hypertension only in presence of genetic defect determining this pathology. Changes in adult HPAS function due to shortage of noradrenaline in the brain in the end of the 1st month of life do not depend on hypertension.     

Vasoactive properties of dihomo-gamma-linolenic acid and series one prostaglandins in a freshwater teleost, Channa maculata

1. Prostaglandins A1, B1, E1 and F1 alpha (2-120 micrograms/kg), arachidonic acid and dihomo-gamma-linolenic acid (0.1-2 mg/kg) were injected intravenously into Channa maculata and changes in arterial blood pressure were recorded. 2. Injection of PGF1 alpha had no significant effect on arterial blood pressure. Injection of PGA1 and PGE1 was followed by dose-dependent hypotension whereas injection of PGB1 elicited significant dose-dependent increase in arterial blood pressure. 3. Both dihomo-gamma-linolenic acid and arachidonic acid were also depressor agents but dihomo-gamma-linolenic acid was more potent. 4. A single bolus intravenous injection of indomethacin (5 mg/kg) or 4 daily intraperitoneal injections (4 x 10 mg/kg) significantly lowered arterial blood pressure. One hour after pre-treatment of indomethacin, the vascular effects of both prostaglandin precursors were abolished. 5. It appears that the vascular effects of prostaglandins in Channa maculata are qualitatively different from those reported for mammals.     

Pressor, tachycardic and behavioral excitatory responses in conscious rats following ICV administration of ACTH and CRF are blocked by naloxone pretreatment

Experiments were conducted to compare the blood pressure and heart rate responses of conscious rats given intracerebroventricular (ICV) injections of adrenocorticotropin (ACTH 1-24) and corticotropin releasing factor (CRF). Under sodium pentobarbital anaesthesia, rats were implanted with a stainless-steel cannula into the lateral cerebral ventricle and had their right femoral artery and vein cannulated. Upon recovery (24-48 hr later) conscious, unrestrained rats were given ICV injections (total volume 5 microliter by gravity flow) of sterile saline, ACTH (1-24) (0.85 and 1.7 nmoles) or CRF (0.55 and 1.1 nmoles) and blood pressure and heart rate were monitored over the next 2 hr (from the abdominal aorta via the femoral arterial catheter). Both ACTH and CRF caused mean arterial pressure (MAP) to increase, which was paralleled with increases in mean heart rate (MHR). Moreover, these elevations in MAP and MHR were temporally associated with excessive grooming (for ACTH) and locomotor activity (for CRF), which occurred before and lasted as long as MAP and MHR were enhanced. Intravenous (IV) pretreatment whereby naloxone was given 10 min before ICV administration of ACTH (1.7 nmoles) or CRF (1.1 nmoles), showed that naloxone blocked the behavioral, pressor and tachycardic effects of both ACTH and CRF. The results demonstrate that the pressor, tachycardic and locomotor effects evoked in conscious rats by ICV administration of ACTH or CRF are antagonized by naloxone and that their hemodynamic changes may, in part, be mediated by prior behavioral activation.     

Changes of mean arterial pressure of the rat resulting from intracereboventricular injections of prostacyclin of 6-keto-prostaglandin F1 Alpha

Repeated intracerebroventicular injections of 1 μg prostacyclin reduce mean arterial pressure of conscious normotensive rats and reverse the elevation of blood pressure of conscious rats resulting from the intraventricular injection of angiotensin II. The reduction of blood pressure of normotensive rats by prostacyclin is enhanced by pretreatment with probenecid, an inhibitor of fatty-acid transport across biological membranes. Although probenecid does not completely inhibit the transport of fatty acids from the brain to the periphery, the greater effectiveness of prostacyclin in probenecid-treated animals suggests that centrally injected prostacyclin need not leak into the periphery to reduce blood pressure. When the dose of prostacyclin is reduced to 100 ng repeated each minute for 10 min, no change of blood pressure of normotensive rats is observed. The failure of the lower dose of prostacyclin to reduce blood pressure may be due to its rapid degradation. Ventricular injections of 6-keto-prostaglandin F_1a, a major product of prostacyclin metaolism, causes an increase of blood pressure which may counteract the action of prostacyclin itself.     

Effect of chronic stress during prepubertal period of life on development of inherited arterial hypertension

The immediate and long-lasting effects of environmental stress during prepubertal life on arterial blood pressure (AP) were studied in rats with inherited stress-induced arterial hypertension (ISIAH) and normotensive Wistar rats. Two models of chronic stress (the 21st-32nd postnatal days) were used: repeated handling and unpredictable stress of daily exposures to a variety of mild physical or psychoemotional stressors. Chronic prepubertal stress did not affect the basal or stress-induced AP levels in young or adult Wistar rats. In ISIAH rats, chronic stress during the early phase of hypertension development did not accelerate its formation and did not augment its manifestation in adults. Moreover, the basal AP was decreased in young and adult ISIAH rats exposed to prepubertal stress as compared to the age-matched controls. AP elevation under acute stress conditions was lower in young ISIAH rats exposed to unpredictable stress. No long-lasting effect of prepubertal stress on acute stress-induced AP elevation in adults was found. The conclusion was drawn that moderate physical and psychoemotional training at prehypertensive stage can positively affect the development of inherited arterial hypertension.     

Brain adrenoreceptors in rats with inherited arterial hypertension due to emotional stress

For the study of genetic and physiological mechanisms of inherited stress-sensitive arterial hypertension, specific binding of ligands of alpha 1-, alpha 2- and beta-adrenoceptors was measured in 2 strains of rats: Wistar normotensive and ISSAH rats (rats with inherited stress-sensitive arterial hypertension). The maximal binding sites (Bmax) and apparent dissociation constants (Kd) were studied with the alpha 1-adrenergic antagonist 3H-prazosin, alpha 2-adrenergic agonist 3H-clonidine and 3H-dihydroalprenolol, a beta 1-receptor antagonist. Four brain regions were investigated: frontal cortex, hypothalamus, pons and medulla oblongata. In comparison with normotensive controls, hypertensive rats had significantly greater density of the alpha 1-adrenoceptors in the medulla oblongata. However, the number of hypothalamic alpha 1-adrenoceptors was significantly reduced in these animals. The same significantly lower alpha 2-adrenoreceptor density was found in the hypothalamus and the pons, and lower, beta-adrenoceptors density in the medulla oblongata. It was concluded that brain adrenoceptors are involved in the mechanisms of development of inherited stress-sensitive hypertensive syndrome.     

Effect of L-DOPA on the Behavioral Activity of Wistar and Spontaneously Hypertensive (SHR) Rats in the Open-Field Test

We studied the effects of i.p. injections of L-DOPA (100 mg/kg) on the behavioral activity of Wistar rats and spontaneously hypertensive rats (SHR) in the open-field test, as well as on the content of catecholamines in the blood plasma of these animals. Prior to the administration of L-DOPA, the total level of locomotor/research activity in SHR was higher, as compared with that in Wistar rats. This was manifested in significantly greater values of the duration of moving of the animals in the center and on the periphery of the field and also in a greater number of rearings on the periphery of this field. At the same time, the episodes of grooming and sitting in Wistar rats were longer. After injections of L-DOPA, interstrain differences increased and became significant for most (9/10) indices of behavioral activity examined in our study. Injections of L-DOPA resulted in significant modifications of the behavioral activity of rats of the above strains, which is evidenced by changes in the number of visits to the peripheral squares of the open field and of rearings in the same field zones. Over repetitive test sessions, interstrain differences between most indices of behavioral activity (except the duration of research activity on the periphery and that of sitting) decreased. Injections of L-DOPA resulted in a significant increase in the content of this agent and dopamine in the blood plasma of rats of both strains; the level of noradrenaline in SHR also increased. The importance of a hereditary factor-determined increase in the activity of catecholaminergic brain systems (first of all, the dopaminergic system) in SHR for the specificity of locomotor behavior of these animals is discussed.     

Vasorelaxant effect of C16-PAF and C18-PAF on renal blood flow and systemic blood pressure in the anesthetized rat

The renal vasoactive and systemic hypotensive effects of platelet activating factor (C16:0-PAF and C18:1-PAF) were examined in anesthetized male Wistar rats. Bolus injections of C16-PAF (0.5-25 ng/kg) and C18-PAF (2.5-200 ng/kg) into the arterial circulation of the kidney produced increases in renal blood flow (6-15%) before causing dose-dependent systemic hypotension (2-64 mmHg). The dose-response curves for renal blood flow and systemic blood pressure generated by intrarenal C18-PAF administration were approximately 7 fold to the right of the dose-response curves generated by C16-DPAF. Intrarenal injections of vehicle or the biologically inactive enantiomer C16-DPAF (25-200 ng/kg) did not affect renal blood flow or systemic blood pressure. These results suggest that C16:0-PAF is a more potent renal vasodilator and hypotensive lipid than C18:1-PAF.     

Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.

We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.     

The brain is one of the sources of L-dihydroxyphenylalanine in systemic circulation in fetuses and neonatal rats

The performed study was aimed at checking our hypothesis that the developing brain is a source of L-dihydroxyphenylalanine (L-DOPA), a precursor of dopamine in the total circulation system. At the initial stage, the L-DOPA concentration in peripheral blood was analyzed at the 18th and 21st embryonal days (E18 and E21), at the 3rd postnatal day (P3), and at the prepubertal period (P30). The highest L-DOPA concentration was revealed at the perinatal period, while decreased 4–12 times for the first month of life. The subsequent analysis of dynamics of the total blood L-DOPA content showed that maintenance of the constant L-DOPA concentration at the perinatal period on the background of a gradual increase of the blood serum volume is due to a rise of its secretion. At the postnatal period (P3–P30), the blood L-DOPA content increased twice in males, whereas it decreased to the same extent in females. Analysis of the L-DOPA concentration in two most important brain centers, hypothalamus and mesencephalon-rhombencephalon, showed its twofold decrease in hypothalamus during E18–E21 of development; then it slightly increased from E21 to P3 and fell 4–5 times by P30. In mesencephalon-rhombencephalon, the L-DOPA concentration was slightly reduced from E18 to E21 (only in females), while on P3 it returned to the E18 level and decreased 7–9 times by P30. The direct proof for the L-DOPA release from the developing brain into the systemic circulation follows from comparison of the blood L-DOPA concentration in shamoperated and encephalectomized rat fetuses after mechanical destruction of neurons of the two abovementioned most important dopaminergic centers. Thus, encephalectomy led to a twofold reduction of the blood L-DOPA concentration (statistically significant differences were observed only in females). Thus, the work presents evidence that the developing brain is one of L-DOPA sources in the total circulation system in rats during prenatal and early postnatal periods of ontogenesis.     

Effect of endothelin-1 on pulmonary resistance in rats

We examined the effect of endothelin-1 (ET-1), a novel 21-residue vasoconstrictor peptide, on pulmonary resistance (RL) in Wistar rats. The lung volume, tracheal flow, and transpulmonary pressure of tracheotomized and paralyzed rats were measured with a fluid-filled esophageal catheter and a pressure-sensitive body plethysmograph. RL was calculated by the method of von Neergaard. The femoral artery was cannulated to measure the mean arterial blood pressure. Intravenous bolus administration of synthetic ET-1 provoked a dose-dependent increase in RL in rats. The bronchoconstricting effect reached maximum at 500 pmol/kg. This bronchoconstriction was observed in less than 5 min, increased up to 15 min, and was sustained for 60 min. ET-1 increased the mean arterial blood pressure in a dose-dependent manner. We conclude that ET-1 is a hitherto unknown potent bronchoconstrictor that has a sustained effect in vivo. The potential physiological and pathophysiological role of this new peptide in the development of respiratory disease warrants further investigation.     

NO mediates effects of estrogen on central regulation of blood pressure in restrained,ovariectomized rats

We tested the hypotheses that estrogen replacement in ovariectomized (OVX) rats attenuates cardiovascular responses to psychological stress and that nitric oxide (NO) in the brain mediates these effects. Female rats were OVX; one group received 17beta-estradiol (OVX-E) for 11-12 days and the other received vehicle (OVX-V). Seven days after OVX, OVX-E and OVX-V rats were chronically instrumented for arterial pressure measurements and intracerebroventricular injections. Later (4-5 days), OVX-E and OVX-V rats received intracerebroventricular injections of NG-nitro-l-arginine (88 microg/kg), an inhibitor of constitutive NO production, or vehicle. Mean arterial pressure (MAP) and heart rate responses were then measured in conscious rats exposed to two cycles of 1-h restraint/1-h rest. We show that MAP responses in restrained OVX-E rats were attenuated both during restraint and during rest. Although inhibition of NO production in the brain had no effect on MAP responses to restraint in OVX-V rats, it augmented responses in restrained OVX-E rats, especially during periods of rest, so that MAPs in restrained OVX-E and OVX-V rats were indistinguishable. Finally, NO levels in hypothalami and brain stems were elevated in restrained OVX-E, but not OVX-V, rats compared with their respective unrestrained controls. These results show that estrogen replacement in OVX rats reduces arterial pressure responses to psychological stress and that these effects are mediated, at least in part, by NO.     

Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase activator, BAY 60-2770, are not dependent on endogenous nitric oxide or reduced heme

4-({(4-Carboxybutyl)[2-(5-fluoro-2-{[4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}methyl)benzoic acid (BAY 60-2770) is a nitric oxide (NO)-independent activator of soluble guanylyl cyclase (sGC) that increases the catalytic activity of the heme-oxidized or heme-free form of the enzyme. In this study, responses to intravenous injections of the sGC activator BAY 60-2770 were investigated under baseline and elevated tone conditions induced by the thromboxane mimic U-46619 when NO synthesis was inhibited by N(ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME), when sGC activity was inhibited by 1H-[1,2,4]-oxadizaolo[4,3]quinoxaline-1-one (ODQ), an agent that oxidizes sGC, and in animals with monocrotaline-induced pulmonary hypertension. The intravenous injections of BAY 60-2770 under baseline conditions caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and no change or small increases in cardiac output. Under elevated tone conditions during infusion of U-46619, intravenous injections of BAY 60-2770 caused larger decreases in pulmonary arterial pressure, smaller decreases in systemic arterial pressure, and increases in cardiac output. Pulmonary vasodilator responses to BAY 60-2770 were enhanced by L-NAME or by ODQ in a dose that attenuated responses to the NO donor sodium nitroprusside. ODQ had no significant effect on baseline pressures and attenuated pulmonary and systemic vasodilator responses to the sGC stimulator BAY 41-8543 2-{1-[2-(fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl}-5(4-morpholinyl)-4,6-pyrimidinediamine. BAY 60-2770 and sodium nitroprusside decreased pulmonary and systemic arterial pressures in monocrotaline-treated rats in a nonselective manner. The present data show that BAY 60-2770 has vasodilator activity in the pulmonary and systemic vascular beds that is enhanced by ODQ and NOS inhibition, suggesting that the heme-oxidized form of sGC can be activated in vivo in an NO-independent manner to promote vasodilation. These results show that BAY 60-2770 and sodium nitroprusside decreased pulmonary and systemic arterial pressures in monocrotaline-treated rats, suggesting that BAY 60-2770 does not have selective pulmonary vasodilator activity in animals with monocrotaline-induced pulmonary hypertension.     

Resetting blood pressure by a closed-loop implanted chip system in normotensive rats

A closed-loop implanted chip system was designed to control blood pressure without using drugs. The chip system instantaneously reset blood pressure by stimulating the left aortic depressor nerve according to the feedback signals of arterial blood pressure. The relationship between pressure signals and frequency of stimulation was identified in vitro and in vivo, and the efficiency of the chip system was evaluated in normal anesthetized Wistar rats. To determine whether the depressor effect of the chip was primarily independent on the bradycardia induced by the resetting, the effects of methyl atropine (1.5 g/kg, iv.) and bilateral vagotomy on depressor effect induced by the chip system were determined, respectively. The results indicated that the chip system worked well. The frequency of stimulus linearly increased following the elevation of pressure from 70 to 160 mm Hg. The frequency of the stimulus reached its maximum (100 Hz) when pressure exceeded 160 mm Hg, and the stimulation stopped when MAP was below 70 mm Hg. There were significant decreases in mean arterial pressure (MAP, -20.0+/-4.4 mm Hg) and heart rate (HR, -43.0+/-10.5 bpm) during the resetting in rats. After resetting, both MAP and HR recovered in a minute without any significant rebound. Pretreatment with either methyl atropine or bilateral vagotomy abolished the bradycardia effect but produced no significant effect on hypotension. The results demonstrated that the chip system successfully reset blood pressure in rats, and that the hypotension induced by the chip system was primarily independent on the bradycardia effect.     

Effect of angiotensin converting enzyme inhibition on renal response to atrial natriuretic factor in rats

Previous studies have shown that atrial natriuretic factor (ANF) inhibits renin secretion whereas cilazapril blocks angiotensin II generation via converting enzyme inhibition. Both agents enhance renal excretory function. The present study was conducted to test whether the renin-angiotension system is involved in the ANF-induced renal effects. ANF was administered to anesthetized normal rats (n = 16) with or without a simultaneous infusion of cilazapril. Single bolus injections of ANF at doses of 2.5 micrograms/kg and 5.0 micrograms/kg significantly decreased mean arterial blood pressure by 6.8 +/- 2.3% and 9.4 +/- 2.2%, respectively. The corresponding increases in glomerular filtration rate were 5.6 +/- 3.7% and 8.4 +/- 2.8%, in absolute sodium excretion were 55.0 +/- 18.5% and 105.2 +/- 39.9%, and in urine flow were 24.8 +/- 9.3% and 35.6 +/- 14.6%. Intravenous infusion of cilazapril (33 micrograms/kg.min) reduced the arterial blood pressure, elevated the glomerular filtration rate and increased sodium and water excretion. The corresponding doses of ANF administration during continuous infusion of cilazapril further decreased blood pressure by 8.3 +/- 1.9% and 10.9 +/- 5.4%, respectively. However, there were no significant changes in the glomerular filtration rate and sodium and water excretion. The failure of ANF to exhibit a renal effect was irrelevant to the lowering blood pressure induced by cilazapril. These results suggest that reduced endogenous angiotensin II generation contributes to the renal, but not the hypotensive, effect of ANF.