Biomedical subjects

C I Johnston

Publications and source records attributed to C I Johnston.

At least 19 recordsLinked to original sources

PubMed1992

Characterization of angiotensin converting enzyme in isolated cerebral microvessels from spontaneously hypertensive and normotensive rats.

OBJECTIVE: Abnormalities in the vascular renin-angiotensin system have been hypothesized to contribute to the pathogenesis and complications of hypertension. In animal models of hypertension, there is wide variation in reported vascular angiotensin converting activity, particularly in cerebral microvessels. In this study, we sought to characterize, quantitate and compare cerebral microvessel angiotensin converting enzyme (ACE) in genetically hypertensive rats and normotensive rats. DESIGN: Brain microvascular ACE from 14-week-old spontaneously hypertensive rats (SHR) was measured and compared with ACE from brain microvessels of normotensive Wistar-Kyoto (WKY) controls. METHODS: Isolated cerebral microvascular ACE was measured using two methods, enzyme kinetic assay or radioligand binding assay. RESULTS: In SHR, cerebral microvessel ACE was of similar activity and concentration and had similar ligand binding affinities to WKY rats. Plasma ACE activity was significantly elevated in WKY rats compared with SHR. CONCLUSION: Cerebral microvascular ACE is similar in SHR and WKY rats. Microvascular ACE is unlikely to participate in the pathogenesis or complications of hypertension in this model.

Animals↗

PubMed1992

Meeting report of the International Society of Hypertension Conference on Hypertension and Diabetes.

Points of agreement: (1) In IDDM, hypertension occurs in patients who have already developed nephropathy, probably in the microalbuminuric phase. (2) Hypertension is an important accelerator of the development of diabetic nephropathy. (3) Hypertension, obesity and NIDDM are often associated, and insulin resistance is commonly observed in all three states. (4) Antihypertensive therapy retards the development of diabetic nephropathy in IDDM and reduces proteinuria in NIDDM. (5) The choice of antihypertensive agent in the diabetic patient must be based upon the efficacy of the drug as well as avoidance of side effects including deleterious influence on glucose, insulin and lipid levels and renoprotection. (6) Carefully conducted long-term comparative trials between different classes of antihypertensive drugs in microalbuminuric IDDM and NIDDM patients are essential. Points of major controversy: (1) Detection of IDDM patients prone to the development of diabetic nephropathy can be performed by measuring specific parameters such as erythrocyte Na(+)-Li+ countertransport activity. (2) Insulin resistance is a pathogenic mechanism rather than purely an association with hypertension and obesity. (3) A certain class of antihypertensive agents--ACE inhibitors--confers a specific renoprotective effect in diabetic nephropathy, in addition to its effects upon systemic blood pressure. (4) Reduction of blood pressure should be considered in the normotensive microalbuminuric diabetic patient. (5) Microalbuminuria is a sufficient 'surrogate endpoint' for the progression of renal failure.

Animals↗

PubMed1992

Steady-state pharmacokinetics and pharmacodynamics of cilazapril in the presence and absence of cyclopenthiazide.

Twenty-two patients with essential hypertension received a single dose of 2.5 mg cilazapril and were then randomised into a double-blind parallel group study to receive either placebo, 1.25 mg cilazapril + 0.5 mg cyclopenthiazide (CPTZ), 2.5 mg cilazapril + 0.5 mg CPTZ, or 2.5 mg cilazapril alone for 1 month. After oral administration of a single dose of 2.5 mg cilazapril, the active diacid cilazaprilat appeared rapidly in the plasma (Tmax 2.0 +/- 0.2 h). With the radioinhibitor assay used in this study, a single elimination phase of cilazaprilat was evident, with a half-life (t1/2) of 2-3 h. At steady state, the pharmacokinetics of cilazaprilat were similar to single-dose administration and were not altered by CPTZ. The Cmax and area under the curve (AUC) of cilazaprilat were directly proportional to dose. Cilazapril administration in the dose range of 1.25-2.5 mg produced a dose-proportional inhibition of angiotensin-converting enzyme (ACE) activity that was maximum 2 h after drug administration. The degree of ACE inhibition correlated with the plasma concentration-time profile of cilazaprilat and the maximum decrease in blood pressure (BP). The EC50 for ACE inhibition by cilazaprilat was 7.7 ng/ml after acute treatment and was not significantly altered during chronic administration or by concomitant administration of CPTZ. There was no evidence of a dose-related antihypertensive effect of cilazapril at steady state and, with the small numbers of subjects used in this study, there was no evidence of 24-h BP control with monotherapy.

Aged↗

PubMed1992

Mesenteric resistance and brain microvascular angiotensin-converting enzyme in the spontaneously hypertensive rat.

1. Angiotensin-converting enzyme (ACE) concentration was measured in mesenteric and brain microvessels from spontaneously hypertensive rats (SHR) and compared with normotensive controls using a specific radioligand binding assay. 2. Plasma angiotensin-converting enzyme activity was similar in SHR (n = 15) and normotensive controls (n = 21; 58 +/- 1 nmol HL/mL per min, vs 64 +/- 6 nmol HL/mL per min). 3. There was no significant difference between the mesenteric vascular angiotensin-converting enzyme radioligand binding site density (Bmax, fmol/mg protein) of SHR and normotensive controls (954 +/- 77 vs 890 +/- 56, P = 0.5, unpaired Student's t-test), despite significant differences in systolic blood pressure (220 +/- 8 mm Hg vs 120 +/- 6 mm Hg respectively, P less than 0.01) and increased mesenteric wet weight to bodyweight ratio in the hypertensive rats (0.28 +/- 0.02 mg/g, n = 5 vs 0.16 +/- 0.02 mg/g, n = 7, P less than 0.01). 4. Brain vascular angiotensin-converting enzyme radioligand binding site density (Bmax, fmol/mg protein) was also similar in SHR and normotensive controls (467 +/- 62, n = 5 vs 497 +/- 64, n = 5, P = 0.7, unpaired Student's t-test). 5. These results demonstrate that vascular angiotensin-converting enzyme concentration is not altered in the SHR and that vascular ACE is not increased in this form of vascular hypertrophy or regulated by the blood pressure level.

Animals↗

PubMed1992

Variation in angiotensin-converting enzyme (ACE) inhibitor affinity at two binding sites on rat pulmonary ACE: influence on bradykinin hydrolysis.

1. ACE from rat lung and testis was characterized by radioligand binding studies using [125I]-Ro 31-8472, the radioiodinated hydroxy derivative of the potent ACE inhibitor cilazaprilat. 2. Analysis of the displacement of [125I]-Ro 31-8472 from ACE by ACE inhibitors of different structure by the LIGAND program was best fitted by a two binding site model for lung ACE and a one binding site model for testis ACE. 3. There was marked variation in ACE inhibitor binding affinity at the two binding sites of lung ACE across the panel of ACE inhibitors studied (equilibrium dissociation constant; Kd; pmol/L) for site one vs site two: cilazaprilat 40 +/- 3 vs 430 +/- 92*; lisinopril 25 +/- 1 vs 848 +/- 107**; and quinaprilat 4 +/- 1 vs 1869 +/- 720; *P less than 0.05; **P less than 0.005, t-test, n = 3). Reduction in binding affinity at site two of lung ACE was related to an increase in ACE inhibitor side chain length or complexity of carboxyl terminal moiety. ACE inhibitor binding affinity at the testis ACE binding site resembled site one of lung ACE. 4. Inhibition of bradykinin hydrolysis by lung ACE in the presence of increasing concentrations of cilazaprilat or quinaprilat was similar (F = 0.64; P greater than 0.05), suggesting that bradykinin cleavage predominates at ACE active site one. 5. The differences in ACE inhibitor affinity at the two ACE active sites has implications in physiological substrate selectivity, and may influence the pharmacodynamic effects of different ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Effect of neutral endopeptidase inhibitor in rats with congestive heart failure.

1. The acute hormonal, renal and haemodynamic effects of SCH 39370, a new neutral endopeptidase (NEP) inhibitor, were evaluated in rats with congestive heart failure (CHF) produced by coronary ligation. 2. Left ventricular systolic pressure and left ventricular end diastolic pressure were significantly decreased by SCH 39370 treatment. 3. SCH 39370 improved cardiac function by increasing cardiac index and decreasing total peripheral resistance. 4. SCH 39370 induced a transient but significant diuresis and natriuresis. 5. These effects were associated with significant increases in urinary atrial natriuretic peptide (ANP) and cyclic GMP excretion, but not with an increase in plasma ANP levels. 6. The results suggest that NEP inhibition may be a new therapeutic method for treating CHF possibly by potentiating the biological activities of endogenous ANP.

Animals↗

PubMed1992

The tissue renin-angiotensin system and its functional role.

1. The components of the renin-angiotensin system exist in many cardiovascular tissues (heart vessels, kidneys, adrenal glands). 2. Angiotensin-converting enzyme (ACE) is similar in somatic cells from all these sites. 3. ACE contains two catalytic sites that have different conformation requirements. This suggests that each site may have different substrates and that specific inhibitors could be developed for each site. 4. The cardiovascular functions of tissue ACE may include the regulation of regional blood flow, modulation of local sympathetic activity, stimulation of hyperplasia and hypertrophy and the mediation of inflammation.

Animals↗

PubMed1992

Acute and chronic effects of angiotensin-converting enzyme inhibitors on tissue angiotensin-converting enzyme.

1. The effects of angiotensin-converting enzyme (ACE) inhibitors on the tissue ACE were assessed by quantitative in vitro autoradiography after acute and chronic administrations of the drugs. 2. Following acute administration of lisinopril, perindopril or benazepril, ACE was markedly inhibited in the lung, kidney and blood vessels but not in the testis. In the brain, ACE was inhibited mainly in structures with a deficient blood brain barrier. 3. High doses of perindopril progressively inhibited ACE in other brain structures. Tissue ACE inhibition persisted after serum levels of the enzyme had returned to control levels. In the case of perindopril, the time course of tissue ACE inhibition correlated with the inhibition of the pressor responses to exogenous angiotensin I. 4. After chronic administration of lisinopril or perindopril for 14 days, a similar pattern of ACE inhibition was observed in the kidney, lung and blood vessels. In the lung, however, lisinopril was found to increase total ACE by 30%, while plasma ACE was increased two-threefold by both lisinopril and perindopril. Testicular ACE remained unaltered by chronic lisinopril treatment. 5. Overall, the changes in tissue ACE after the administration of inhibitors more closely parallel the drugs' biological effects than changes in plasma ACE or drug levels. ACE in the testis and brain is protected by permeability barriers that limit access of the drugs.

Administration, Oral↗

PubMed1992

Atrial natriuretic peptide is involved in the ACTH response to stress and glucocorticoid negative feedback in the rat.

The role of atrial natriuretic peptide (ANP) in the ACTH response to stress and the glucocorticoid negative feedback control of ACTH release was investigated in adult male homozygous Brattleboro and adrenalectomized Wistar rats respectively, using the technique of immunoneutralization. The relatively low ACTH response to stress and the lack of arginine vasopressin make the homozygous Brattleboro rat a more rigorous and simpler preparation in which to test the hypothesis that ANP is involved in the ACTH response to stress. In both sets of experiments, blood sampling and injection of sheep anti-ANP or control serum were carried out in conscious animals through intra-atrial cannulae implanted 2 days previously under halothane anaesthesia. A 30-s exposure to ether resulted in a brisk twofold increase in the plasma ACTH concentrations in homozygous Brattleboro rats infused with anti-ANP, but not control serum. The injection of either dexamethasone, a potent glucocorticoid receptor agonist, or corticosterone resulted in a rapid and marked reduction in the plasma concentrations of ACTH in Wistar rats which had been adrenalectomized, under halothane anaesthesia, at least 21 days before experimentation. The inhibitory action of dexamethasone, but not corticosterone, was significantly reduced in animals infused with anti-ANP serum. These results show that the inhibition of ANP release into hypophysial portal blood is probably important for triggering the ACTH response to stress and that ANP may play a role in corticosteroid negative feedback control of ACTH release mediated by type II (glucocorticoid) receptors.

Adrenalectomy↗

PubMed1992

Two binding sites on angiotensin-converting enzyme: evidence from radioligand binding studies.

Purified angiotensin-converting enzyme (ACE) from rat lung and testis, membrane preparations of ACE from lung, kidney, and testis, and ACE from plasma were used in radioligand binding studies, to seek evidence for two binding sites in ACE of somatic origin, as predicted by molecular biology studies. 125I-Ro 31-8472, a radioiodinated hydroxy derivative of cilazaprilat, and 125I-351A, a radioiodinated p-hydroxybenzamidine analogue of lisinopril, were used as radioligands. Autoradiographic study of renal ACE using 125I-Ro 31-8472 or 125I-351A showed the same distribution of radioligand binding across kidney sections and identical radioligand binding for purified lung and testis ACE by Western blot, confirming that the same protein bound both radioligands. Analysis of displacement of 125I-Ro 31-8472 binding from ACE by ACE inhibitors 351A and lisinopril yielded biphasic curves for pulmonary, renal, and plasma ACE and a monophasic curve for ACE from the testis. Analysis by LIGAND suggested two binding sites in ACE from plasma or somatic sources and one binding site in ACE of testicular origin, as predicted by molecular biology studies. Displacement of 125I-351A binding from lung and testis ACE by Ro 31-8472 and 351A was monophasic. LIGAND analysis revealed interaction with a single class of binding sites on lung and testis ACE, in agreement with previous studies using 125I-351A. Equilibrium dissociation constants (Kd) for the carboxyl-terminal (KdI) and amino-terminal (KdII) binding sites of purified ACE, using 125I-Ro 31-8472, were similar for Ro 31-8472 (lung kdI, 65 +/- 7 pM; KdII, 175 +/- 38 pM) but were clearly different for 351A (lung KdI, 19 +/- 2 pM; KdII, 2771 +/- 489 pM; p less than 0.01). Cell membrane-associated somatic ACE and plasma ACE, which is devoid of a carboxyl-terminal hydrophobic anchor region, had similar absolute values and differences in 351A binding affinities at the two ACE binding sites. Kd in testis was 46 +/- 6 pM for Ro 31-8472 and 16 +/- 3 pM for 351A, corresponding to estimates at the carboxyl-terminal binding site of somatic ACE. The 65-200-fold reduction in 351A binding affinity at the amino binding site may limit the detection of two binding sites on somatic ACE by 125I-351A radioligand binding analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Franz Volhard Lecture. Renin-angiotensin system: a dual tissue and hormonal system for cardiovascular control.

BACKGROUND: The renin-angiotensin system is both a circulating and a local tissue hormonal system. All components of the renin-angiotensin system have been found in important cardiovascular structures, including the heart, vessels, brain, kidney and adrenal gland. The angiotensin converting enzyme (ACE) is the final step in the enzymatic cascade of the renin-angiotensin system, which converts angiotensin in both the circulation and the tissues. IMPORTANCE OF ACE CATALYTIC SITES: ACE is predominantly an ectoenzyme with a bilobed homodimer extracellular portion, a short transmembrane span and a small intracellular extension. ACE contains two catalytic sites, one on each lobe. There is evidence that these catalytic sites may differ in several properties and may have different conformational requirements. This raises the possibility that there may be different endogenous substrates for each site and it may be feasible to design more specific ACE inhibitors that inhibit only one catalytic site. CARDIOVASCULAR ROLE OF LOCAL RENIN-ANGIOTENSIN SYSTEM: The physiological cardiovascular functions of the tissue renin-angiotensin system may include regulation of regional blood flow, modulation of local sympathetic activity and interaction with the endothelium. There is increasing evidence that the local renin-angiotensin system may be involved in the maintenance of cardiovascular structure and repair. ACE is increased in many forms of vascular and cardiac hypertrophy and the administration of ACE inhibitors has led to regression of hypertrophy. Many of the beneficial effects of ACE inhibitors may be due to inhibition of the local renin-angiotensin system. ACE INHIBITION FOLLOWING MYOCARDIAL INJURY: The local renin-angiotensin system may also be involved in the response to injury and in the inflammatory response. ACE is known to be increased in granulomas, it is expressed on monocytic macrophages and fibroblasts and many of the peptides involved in the inflammatory response (bradykinin, substance P, enkephalins) can act as ACE substrates. Following an acute myocardial infarct, ACE is increased in the myocardial scar and in the hypertrophying cardiac muscle. This provides a possible mechanism for the beneficial effect of ACE inhibitors in postmyocardial infarction trials. NON-CARDIOVASCULAR SYSTEM: Neither the function of the renin-angiotensin system in the brain and non-cardiovascular tissues nor its role in the pathophysiology of hypertension are known as yet.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1979

Long-term effects of captopril (SQ14 225) on blood-pressure and hormone levels in essential hypertension.

Captopril, an orally active angiotensin-converting enzyme (ACE) inhibitor, was effective in the long-term reduction of blood-pressure in 17 patients with essential hypertension. The addition of hydrochlorothiazide produced a further hypotensive effect, and the combined treatment produced satisfactory control of the blood-pressure for eight months. Captopril prevented and reversed the secondary hyperaldosteronism and hypokalaemia induced by simultaneous diuretic administration, thus eliminating the need for potassium supplements. The fall in plasma-angiotensin-II and urinary aldosterone and rise in angiotensin I and plasma-renin provide biochemical evidence that captopril inhibits ACE in vivo. No change in circulating venous bradykinin levels could be detected. The hypotensive action of captopril is not mediated by changes in blood-bradykinin but may involve inhibition of the renin-angiotensin and kallikrein-kinin systems locally within the kidneys or blood vessels.

Adult↗

PubMed1979

Hormonal changes with long-term converting-enzyme inhibition by captopril in essential hypertension.

1. Captopril was shown to be as effective as hydrochlorothiazide in lowering the blood pressure in patients with moderately severe essential hypertension. 2. With the combination of captopril and hydrochlorothiazide satisfactory control of blood pressure was maintained over 8 months. 3. Inhibition of angiotensin converting enzyme by captopril in man was associated with falls in plasma angiotensin II and urinary aldosterone and rises in angiotensin I and plasma renin. 4. No change in venous concentrations of bradykinin could be demonstrated during therapy. 5. Captopril attenuated the hyperaldosteronism and hypokalaemia associated with diuretic therapy.

Adult↗

PubMed1979

Individual neurophysin concentrations in the pituitary and circulation of humans.

Specific, homologous human neurophysin I and II radioimmunoassays were established and used to measure the individual, immunoreactive neurophysin concentrations in human plasma. Circulating levels of human neurophysin I in normal individuals were less than 1 ng/ml and neurophysin II levels were 1-2 ng/ml. During dehydration, there was a significant rise in plasma neurophysin I, together with an increase in neurophysin II. Haemorrhage also was associated with a rise in plasma neurophysin I and II, but the percent increase was greater for I than II. In two subjects in whom nicotine inhalation caused a rise in plasma neurophysin I, there was no detectable increase in plasma neurophysin II. These stimuli which have been reported to release vasopressin from the posterior pituitary also are associated with the differential release of neurophysin I. Plasma neurophysin II levels could more clearly be shown to rise independently of plasma neurophysin I during events thought to be related to oxytocin release. Plasma neurophysin II levels were significantly elevated in women taking oral contraceptives. Similarly during pregnancy there was a progressive rise in plasma neurophysin II concentration which was proportional to the period of gestation. Plasma neurophysin II concentrations in seven of fifteen nursing women rose significantly during suckling. There was no detectable change in plasma neurophysin I concentrations during any of these events. Plasma neurophysin I and II levels were both significantly elevated in fourteen patients with chronic renal failure and rose over haemodialysis, suggesting that the kidney may be the major route of clearance of the neurophysins. In humans the independent release of neurophysin II was associated with stimuli thought to release oxytocin, but neurophysin I showed only a differential release compared to neurophysin II in vasopressin stimulated events.

Contraceptives, Oral↗

PubMed1979

Acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis in the dog.

1. The acute renal haemodynamic and renin-angiotensin system responses to graded renal artery stenosis were studied in chronically instrumented, unanaesthetized dogs. 2. Stenosis was induced over 30 sec by inflation of a cuff around the renal artery to lower distal pressure to 60, 40 or 20 mmHg, with stenosis maintained for 1 hr. This resulted in an immediate fall in renal vascular resistance, but over the next 5--30 min both resistance and renal artery pressure were restored back towards prestenosis values. Only transient increases in systemic arterial blood pressure and plasma renin and angiotensin levels were seen with the two milder stenoses. Despite restoration of renal artery pressure, renal blood flow remained reduced at all grades of stenosis. 3. Pre-treatment with angiotensin I converting enzyme inhibitor or sarosine1, isoleucone8 angiotensin II greatly attenuated or abolished the restoration of renal artery pressure and renal vascular resistance after stenosis, and plasma renin and angiotensin II levels remained high. Renal dilatation was indefinitely maintained, but the normal restoration of resistance and pressure could be simulated by infusing angiotensin II into the renal artery. 4. The effective resistance to blood flow by the stenosis did not remain constant but varied with changes in the renal vascular resistance.

Angiotensin II↗

PubMed1979

Decreased cardiac beta-adrenergic receptors in deoxycorticosterone-salt and renal hypertensive rats.

The development of experimental deoxycorticosterone-salt (DOCA-salt) and renal artery clip hypertension in rats is associated with alterations in the sensitivity of the myocardium to adrenergic stimulation. We studied beta-adrenergic receptors and isoproterenol-stimulated adenylate cyclase in myocardial membranes from hypertensive rats to determine whether this altered sensitivity is associated with any change in beta-adrenergic receptors. The specific binding of the beta-adrenergic antagonist, 125I-iodohydroxybenzylpindolol, was used to measure numbers and affinities of receptors in myocardial membrane preparations. Cardiac membranes from both DOCA-salt and renal hypertensive rats showed significantly fewer beta-receptors than did membranes from control, normotensive rats. Receptor affinity remained unchanged. This decrease was from 110 +/- 19 to 49 +/- 5 fmol/mg protein for DOCA-salt hypertension and from 110 +/- 18 to 75 +/- 16 fmol/mg protein for renal artery clip hypertension. Isoproterenol-stimulated adenylate cyclase activity also was lower in membranes from hypertensive rats, whereas basal and fluoride-stimulated activities were unchanged.

4-Nitrophenylphosphatase↗

PubMed1979

Plasma vasopressin and human neurophysins in physiological and pathological states associated with changes in vasopressin secretion.

Using sensitive specific RIAs for vasopressin (AVP) and the two major human neurophysins, the relationship between AVP and the individual human neurophysins was investigated in man by measuring changes in plasma concentrations in physiological and pathological states known to be associated with changes in AVP secretion. Dehydration, water loading, and hemorrhage produced small but significant changes in plasma AVP concentrations without changes in the individual human neurophysins. In response to the stimulus of cigarette smoke inhalation, large parallel changes in plasma AVP and human neurophysin I (HNPI) levels were seen without change in plasma human neurophysin II (HNPII) levels. In the pathological states of diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion,the observations more strongly supported a specific association between AVP and NHPI. In eight patients with central diabetes insipidus, plasma AVP and HNPI levels were low or undetectable, while plasma HNPII levels were normal. There was a clear distinction of both plasma AVP and HNPI levels in patients with central diabetes insipidus and those in patients whti nephrogenic diabetes insipidus. In 14 patients with the syndrome of inappropriate antidiuretic hormone secretion due to causes other than ectopic AVP production from tumors, plasma AVP and HNPI levels were elevated or normal, while plasma HNPII levels were normal. There was a highly significant positive correlation (r = 0.99) between plasma AVP and HNPI levels in these patients, with a 1:1 molar ratio. These data suggest that the secretion of AVP and HNPI in man are functionally related, while the secretion of HNPII is independent of AVP secretion.

Adolescent↗

PubMed1979

Responses of the renin-angiotensin system and kallikrein-kinin system to sodium and converting enzyme inhibitor (SQ 14,225).

Plasma renin activity, blood angiotensin I, urinary kallikrein and blood bradykinin levels have been measured concurrently in rats over a range of daily sodium intake. Plasma renin activity, blood angiotensin I levels and urinary kallikrein were significantly increased by the low sodium diet (0.02 mmole per day). Bradykinin levels did not change. Plasma renin and blood angiotensin I were closely linearly related over the range of sodium intakes. Both were associated positively with urinary kallikrein excretion. Converting enzyme inhibition caused prompt, significant changes in plasma renin activity, endogenous circulating angiotensin I, and bradykinin. The changes in circulating hormone levels were dose dependent. Blood angiotensin I levels showed a greater responsiveness than blood bradykinin levels. Plasma renin activity and blood angiotensin I levels are closely related after converting enzyme inhibition. Both increased plasma renin, and impaired clearance of angiotensin I may contribute to blood angiotensin I levels. Difference in responsiveness of blood angiotensin I and blood bradykinin levels after inhibition suggests that other independent controls of the circulating levels of these hormones exist.

Angiotensin I↗