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At least 19 recordsLinked to original sources
PubMed1977

Effects of angiotensin III (DES-1-asp-angiotensin II) and angiotensin III analogue (DES-1-asp-8-ile-angiotensin II) upon adrenal steroidogenesis and blood pressure.

Effects of angiotensin III and angiotensin III analogue upon adrenal steroidogenesis and blood pressure were studied in rats, rabbits and a man. Pressor effect of angiotensin III was about one fifth of that of angiotensin II in all the species. Degradation rate of pressor effect of angiotensin III in plasma was more rapid than that of angiotensin II. Different from the effects of angiotensin III upon blood pressure, its effect upon aldosterone was similar to that of angiotensin II. The effect of angiotensin III upon other adrenal steroids, such as DOC and cortisol, however, seemed to be slightly less than that of angiotensin II. Angiotensin III producted an additive effect to that of ACTH, but it didn't produce an additive effect to that of angiotensin II. Angiotensin III analogue, itself, stimulated adrenal steroidogenesis, but it inhibited the effects of angiotensin III and angiotensin II upon aldosterone. Effects of ACTH upon plasma DOC and cortisol were not inhibited by angiotenesin III analogue, but the effect of ACTH upon aldosterone was blunted slightly.

Adrenal Cortex↗
PubMed1978

The half-lives of angiotensin II, angiotensin II-amide, angiotensin III, Sar1-Ala8-angiotensin II and renin in the circulatory system of the rat.

1. Methods are described for estimating the half-life of angiotensin analogues and renin in the rat, from the time course of the blood pressure changes they evoke. 2. The following half-life values were measured: angiotensin II, 16 +/- 1 sec; angiotensin III, 14 +/- 1 sec; angiotensin II-amide, 15 +/- 1 sec; Sar1-Ala8-angiotensin II, 6.4 +/- 0.6 min; renin, 3.0 +/- 0.4 min. The distribution volume of angiotensin was found to be 18 ml./kg body wt. 3. It is inferred that the Asp1 residue does not reduce the rate of angiotensin II catabolism, but that substitution of this residue by sarcosine may inhibit catabolism while substitution by asparagine has no effect. 4. Five experimental criteria were identified which indicate that these methods give reliable estimates of the half-life. It is suggested that these results are more accurate than most previous half-life estimates. 5 When tachyphylaxis to angiotensin II-amide occurs, the pressor activity of the plasma is not reduced.

Angiotensin Amide↗
PubMed1994

Characterization of a new angiotensin antagonist selective for angiotensin-(1-7): evidence that the actions of angiotensin-(1-7) are mediated by specific angiotensin receptors.

In this study we describe a new angiotensin antagonist [Asp1-Arg2-Val3-Tyr4-Ile5-His6-D-Ala7, (A-779)] selective for the heptapeptide angiotensin-(1-7) [Ang-(1-7)]. A-779 blocked the antidiuretic effect of Ang-(1-7) in water-loaded rats and the changes in blood pressure produced by Ang-(1-7) microinjection into the dorsal-medial and ventrolateral medulla. In contrast, A-779 did not change the dipsogenic, pressor, or myotropic effects of angiotensin II (Ang II). Also, A-779 did not affect the antidiuretic effect of vasopressin or the contractile effects of angiotensin III, bradykinin, or substance P on the rat ileum. In the rostral ventrolateral medulla, the pressor effect produced by Ang-(1-7) microinjection was completely blocked by A-779 but not by AT1 or AT2 receptor antagonists (DUP 753 and CGP 42112A, respectively). Conversely, the pressor effect produced by Ang II was not changed by A-779 but was completely blocked by DUP 753. Binding studies substantiated these observations: A-779 did not compete significantly for 125I-Ang II binding to adrenocortical membranes at up to a 1 microM concentration. Low affinity binding was also observed in adrenomedullary membranes with an IC50 greater than 10 microM. Our results show that A-779 is a potent and selective antagonist for Ang-(1-7). More importantly, our data indicate that specific angiotensin receptors mediate the central and peripheral actions of Ang-(1-7).

Adrenal Glands↗
PubMed2000

Angiotensin-converting enzyme-independent angiotensin formation in a human model of myocardial ischemia: modulation of norepinephrine release by angiotensin type 1 and angiotensin type 2 receptors.

Angiotensin II (Ang II) promotes norepinephrine (NE) release from cardiac sympathetic nerve endings. We assessed in a human model in vitro whether locally formed Ang II contributes to NE release in myocardial ischemia. Surgical specimens of human right atrium were incubated in anoxic conditions. After 70 min of anoxia, NE release (carrier-mediated; caused by NE transporter reversal) was 8-fold greater than normoxic release. Angiotensin-converting enzyme inhibition with enalaprilat failed to reduce anoxic NE release. In contrast, prevention of chymase-dependent Ang II formation with chymostatin, Bowman-Birk inhibitor, or alpha(1)-antitrypsin significantly inhibited anoxic, but not exocytotic, NE release. Two mast-cell stabilizers, cromolyn and lodoxamide, markedly reduced NE release, implicating cardiac mast cells as a major source of chymase. Angiotensin type 1 receptor (AT(1)R) blockade with EXP3174 inhibited NE release, whereas angiotensin type 2 receptor (AT(2)R) blockade with PD123319 did not. Interestingly, PD123319 reversed the inhibitory effect of EXP3174. Furthermore, synergisms were uncovered between EXP3174 and an AT(2)R agonist, and between EXP3174 and a Na(+)/H(+) exchanger inhibitor. Thus, angiotensin-converting enzyme-independent Ang II formation via chymase is important for carrier-mediated ischemic NE release in the human heart. Locally generated Ang II promotes NE release by acting predominantly at AT(1)Rs, which are likely coupled to the Na(+)/H(+) exchanger. Effects of Ang II at AT(2)Rs, seemingly opposite to those resulting from AT(1)R activation, are uncovered when AT(1)Rs are blocked. Because NE release is associated with coronary vasoconstriction and arrhythmias, and mast-cell density and chymase content increase in the ischemic heart, the notion that chymase-generated Ang II plays a major role in carrier-mediated NE release may have important clinical implications.

Aged↗
PubMed1997

The renin-angiotensin system and vascular function. The role of angiotensin II, angiotensin-converting enzyme, and alternative conversion of angiotensin I.

The renin-angiotensin system has been implicated in vascular function and disease. Angiotensin-converting enzyme and angiotensin II are believed to be the most important components. However, alternative factors, such as angiotensin-I/II-(1-7) and chymase, have also been shown to be of significance in animal models. In this paper, we review some facts and provide additional proof for the functional significance of angiotensin-I/II-(1-7) and chymase in humans.

Angiotensin I↗
PubMed1976

Stimulating effects of angiotensin I, angiotensin II and des-Asp1-angiotensin II on steroid production in vitro and its inhibition by Sar1-Ala8-angiotensin II.

Two of the agents known to block the renin-angiotensin-aldosterone system, namely Sar1-Ala8-angiotensin II and the nonapeptide SQ 20881, have been used to clarify the role of angiotensin II (AII) and its cogeners upon the steroidogenesis in isolated fasciculata cells from bovine adrenal tissue. It could be concluded that: (1) des-Asp1-angiotensin II is as active as AII on steroidogenesis from bovine fasciculata cells; (2) angiotensin I, although less potent, stimulates steroid production without being converted to AII or des-Asp1-AII, and (3) Sar1-Ala8-AII inhibits all three peptides in a competitive manner. The presence of a common receptor for all these three peptides is suggested.

Adrenal Cortex Hormones↗
PubMed1990

Quantitative evidence of peripheral conversion of angiotensin within the human leg: effects of local angiotensin-I administration and angiotensin-converting enzyme inhibition on regional blood flow and angiotensin-II balance across the leg.

The renin-angiotensin system relevantly contributes to the maintenance of systemic vascular tone and there is experimental evidence that large amounts of angiotensin-converting enzyme (ACE) are present in peripheral vascular tissues, including resistance vessels. To determine and quantify peripheral vascular conversion of angiotensin-I (ANG-I) to angiotensin-II (ANG-II) across the human leg, the response of regional blood flow to local regional intra-arterial infusion of ANG-I and change in associated ANG-II balance were evaluated during ANG-I infusion and following additional ACE inhibition. Ten sodium-loaded healthy men were enrolled in the study. Following cannulation of both femoral arteries and the right femoral vein, leg blood flow was determined (indocyanine-green dye-dilution method) at baseline conditions and during constant intra-arterial infusion of haemodynamically ineffective doses of ANG-I as well as following concomitant intra-arterial administration of low doses of the non-sulfhydril ACE inhibitor cilazapril. From the transfemoral arterio-venous differences in ANG-II plasma concentrations and the corresponding regional blood (plasma) flow, the ANG-II balance across the leg was calculated. Systemic blood pressure did not change throughout the trial, indicating that no major systemic effects were present during ANG-I infusion or concomitant ACE inhibition. Moreover, arterial ANG-II plasma concentrations were not significantly changed by ANG-I infusion. Leg blood flow decreased to below baseline values following ANG-I infusion, increasing again then in a dose-dependent manner during concomitant cilazapril administration. The calculated baseline ANG-II balance across the leg revealed a net extraction in 6 out of 10 subjects and a net ANG-II formation in 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Losartan, a specific angiotensin II receptor antagonist, increases angiotensin I and angiotensin II release from isolated rat hind legs: evidence for locally regulated renin-angiotensin system in vascular tissue.

The effect of Losartan (10(-9) to 10(-6) M) on angiotensins I and II release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal and bilaterally nephrectomized rats. Losartan increased dramatically both angiotensins I (Ang I) and II (Ang II) release in a dose-dependent fashion; the maximal percent increment in Ang I and Ang II release evoked by Losartan (10(-6) M) was about +380% and +160%, respectively, in normal rat hind legs. In nephrectomized animals, Losartan elicited a marked increase in both peptides dose-dependently. There was a highly positive correlation between the released amounts of Ang I and that of Ang II altered by Losartan in either normal (r = 0.954) or nephrectomized rats (r = 0.923). These results not only confirm the existence of a functional renin-angiotensin system in vascular tissues, but also suggest that the system is regulated by locally generated Ang II.

Angiotensin I↗
PubMed1977

Stimulation of corticosteroid biosynthesis by angiotensin I [des-asp1]angiotensin I, angiotensin II and [des-asp1]-angiotensin II in bovine adrenal fasciculata cells.

The effect of angiotensin I (AI), angiotensin II (AII), [des-asp1]AI, [des-asp1]AII and [des-asp1-arg2]AII on corticosteroid production in isolated fasciculata cells from bovine adrenals has been studied. AII and [des-asp1]AII in concentrations ranging from 10(-9)M to 10(-6)M had a potent stimulatory effect on steroid biosynthesis. The dose-response curves for both peptides were identical. AI was about 3 times less potent than AII and [des-asp1]AII. The effect of AI was not due to its conversion to AII. [Des-asp1]AI was as active as AI. No significant conversion to [des-asp1]AII was observed. [Des-asp1-arg2]AII had only a minimal effect on steroidogenesis. The structural analog [sar1,-ala8]AII inhibited all angiotensins specifically and competitively. The affinity of the cellular binding site was higher for AII and [des-asp1]AII than for [sar1,ala8]ALL, but lower for AI and [des-asp1]AI than for the inhibitor. Combination of submaximal doses of AI and AII resulted in an additive effect on steroid production. By contrast, combination of maximal doses of both peptides had the same effect as AII alone. These data demonstrate a potent steroidogenic activity for AII as well as AI, [des-asp1]AI and [des-asp1]AII in bovine adrenal fasciculata cells. A common receptor site for all four peptides is suggested.

Adrenal Cortex Hormones↗
PubMed2001

Effects of angiotensin IV and angiotensin-(1-7) on basal and angiotensin II-stimulated cytosolic Ca2+ in mesangial cells.

This study analyzed the influence of two main metabolites of angiotensin II, angiotensin IV and angiotensin-(1-7), on basal and angiotensin II-dependent [Ca2+](i) in rat mesangial cells. Angiotensin IV behaved as a weak agonist. Its effects were abolished by angiotensin AT(1) receptor antagonists. Treatment with angiotensin II abolished the effect of a subsequent treatment with angiotensin IV whereas two successive angiotensin IV-dependent [Ca2+](i) peaks were obtained. Angiotensin II increased [Ca2+](i) in a Ca2+-free medium whereas angiotensin IV was inactive. Leucine-valine-valine-hemorphin 7, a hemorphin specific for the angiotensin AT(4) receptor, was devoid of any agonistic or antagonistic effect. In contrast, angiotensin-(1-7), if without influence on basal [Ca2+](i), inhibited angiotensin II- and angiotensin IV-dependent [Ca2+](i) increases. Total inhibition of the angiotensin IV effect was obtained whereas association of angiotensin-(1-7) to 8-(NN-diethylamino)-octyl-3,4,5-trimethoxybenzoate, an inhibitor of inositol phosphate-mediated Ca2+ release, was necessary to suppress the effect of angiotensin II. These results provide evidence that angiotensin II metabolites may participate in the control of [Ca2+](i) in mesangial cells at the initial stage of binding to the angiotensin AT(1) receptors.

Angiotensin I↗
PubMed1995

Effects of des-Asp-angiotensin I on the contractile action of angiotensin II and angiotensin III.

Nanomolar concentrations of des-Asp-angiotensin I potentiated the contractile action of angiotensin II on the rabbit aortic ring but attenuated the contractile action of angiotensin III in the same tissue. Indomethacin had no effect on the potentiation of angiotensin II but inhibited the attenuation of angiotensin III. The action of angiotensin II, angiotensin III and des-Asp-angiotensin I was not inhibited by (S)-1-}[4-(dimethylamino)-3-methylphenyl]methyl}-5-(diphenylacetyl )-4,5,6, 7-tetrahydro-1H-imidazo-[4,5-c]pyridine-6-carboxylic acid, ditrifluoroacetate, dihydrate (PD123319), an angiotensin AT2 receptor antagonist. The data show that angiotensin II and angiotensin III act on different subclasses of angiotensin receptors and that their actions are differentially modulated by des-Asp-angiotensin I. The data also indicate the possibility that des-Asp-angiotensin I is a functional peptide that modulates the contractile action of the two angiotensins at sub-nanomolar concentrations.

Angiotensin I↗
PubMed2004

Single versus dual blockade of the renin-angiotensin system (angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers) in diabetic nephropathy.

PURPOSE OF REVIEW: Antihypertensive treatment has improved renal prognosis and survival in diabetic nephropathy. The present review summarizes the current status of blockade of the renin-angiotensin system in diabetic nephropathy. Since the current treatment strategies reduce, but do not prevent, the progression of kidney disease, the research focus is directed towards the potential renoprotective effects of dual blockade of the renin-angiotensin system using both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. RECENT FINDINGS: Angiotensin-converting enzyme inhibitors are now a first-line therapy for patients with type 1 diabetes and diabetic nephropathy, whereas in patients with type 2 diabetes, angiotensin II receptor blockers have been shown to protect the kidney. The optimal doses of both types of drug remain to be determined, and the efficacy of each medication needs to be compared both in patients with type 1 diabetes and in those with type 2 diabetes. Experimental studies suggests that dual blockade of the renin-angiotensin system may offer additive beneficial effects relative to angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. In agreement with this, short-term studies of patients with diabetes have suggested that further renal and cardiovascular protection is achieved using dual blockade of the renin-angiotensin system. Long-term trials will finally define the role of this new treatment concept in diabetic nephropathy. SUMMARY: All diabetic patients with elevated urinary albumin excretion need blockade of the renin-angiotensin system by either angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. In addition, albuminuria and elevated blood pressure should be treated aggressively with a view to achieving blood pressure readings below 130/80 mmHg and albuminuria values of less than 300 mg/24 h; this often necessitates multi-pharmacy. Dual blockade of the renin-angiotensin system may be helpful in reaching these goals in treatment-resistant patients with diabetic nephropathy.

Albuminuria↗
PubMed2001

The differential effect of angiotensin II and angiotensin 1-7 on norepinephrine, epinephrine, and dopamine concentrations in rat hypothalamus: the involvement of angiotensin receptors.

Angiotensin 1-7 has been recently claimed the active member of the angiotensins' family. In the present study we compared the effect of angiotensin II and angiotensin 1-7 on the concentration of dopamine, serotonin, epinephrine, and norepinephrine and some of their metabolites in the rat hypothalamus, where the levels of angiotensins are particularly high. Intracerebroventricular injection of angiotensin II, but not angiotensin 1-7, time-dependently elevated the levels of both epinephrine (p < 0.05) and norepinephrine (p < 0.05) in the hypothalamus and both effects could be prevented by intracerebroventricular injection of either AT(1) (candesartan), AT(2) (PD123319) or AT(1-7) (A-779) receptor antagonist. Neither angiotensin II nor angiotensin 1-7 produced any changes in the level of dopamine, dihydroxyphenylacetic acid, homovanilic acid, serotonin, 5-hydroxyindoleacetic acid, or tryptophan at any time point in comparison with the control groups. However, AT(1) but not AT(2) receptor blockade, unmasked the stimulatory effect of angiotensin 1-7 on dopamine concentration in the hypothalamus. Thus, angiotensin II and its active metabolite angiotensin 1-7 regulate selectively, albeit differentially, adrenergic, noradrenergic and dopaminergic systems in the hypothalamus, the effects that involve AT(1), AT(2) and AT(1-7) angiotensin receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2004

Effect of reduced angiotensin-converting enzyme gene expression and angiotensin-converting enzyme inhibition on angiotensin and bradykinin peptide levels in mice.

There is uncertainty about the contribution of angiotensin-converting enzyme (ACE) to angiotensin II formation, with recent studies suggesting that non-ACE enzymes may be the predominant pathway of angiotensin II formation in kidney, heart, and lung. To investigate the role of ACE in angiotensin II formation, we measured angiotensin I and II levels in blood, kidney, and heart of 2 mouse genetic models (ACE.1 and ACE.4) of reduced somatic ACE gene expression and in blood, kidney, heart, lung, adrenal, and brain of mice administered the ACE inhibitor lisinopril. We also measured the levels of bradykinin (1-9) and its ACE metabolite bradykinin (1-7). Reduced ACE gene expression and ACE inhibition had similar effects on angiotensin and bradykinin peptide levels. Angiotensin II levels were reduced by 70% to 97% in blood, 92% to 99% in kidney, 93% to 99% in heart, 97% in lung, and 85% in adrenal and brain. The marked reductions in angiotensin II/angiotensin I ratio indicated that ACE was responsible for at least 90% of angiotensin I conversion to angiotensin II in blood, kidney, heart, lung, and brain, and at least 77% in adrenal. Blood bradykinin (1-9) levels were increased 6.4-fold to 8.4-fold. Heart bradykinin (1-9) levels were increased in ACE.4 mice and the bradykinin (1-7)/bradykinin (1-9) ratio was reduced in kidney and heart of ACE.4 mice and heart of lisinopril-treated mice. These studies demonstrate that ACE is the predominant pathway of angiotensin II formation in blood and tissues of mice and plays a major role in bradykinin (1-9) metabolism in blood and, to a lesser extent, in kidney and heart.

Adrenal Glands↗
PubMed1999

Interrupting the renin-angiotensin system: the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the treatment of hypertension.

The renin-angiotensin system has two roles in clinical hypertension: its vasoconstrictor properties directly govern blood pressure, and its actions on arterial smooth muscle, connective tissue, and endothelial integrity affect cardiovascular prognosis. Additionally, the direct actions of angiotensin II on the function and structure of the heart and renal vasculature influence clinical events. Angiotensin-converting enzyme (ACE) inhibitors have produced functional and clinical outcome benefits in clinical trials of patients with congestive heart failure, systolic dysfunction after myocardial infarction, and diabetic nephropathy. Similar favorable trends have been noted in observational studies in hypertension. Because such enzymes as chymase can substitute for ACE, the ACE inhibitors may not completely block angiotensin II formation, although they enhance bradykinin accumulation and secondarily stimulate nitric oxide and vasodilatory prostaglandins. Angiotensin II receptor blockers (ARB) selectively block the angiotensin II type 1 (AT1) receptor that not only mediates the known effects of angiotensin II but, according to recent reports, might be responsible for sequestering angiotensin II molecules in renal and cardiac cells. Moreover, by increasing plasma concentrations of angiotensin II, the ARB stimulate the unblocked angiotensin II type 2 (AT2) receptors, which-if they exist in meaningful numbers in human hypertension-mediate additional vasodilatory and antiproliferative effects. The contrasting actions of these two classes of drugs might be clinically relevant. For example, they may have additive antihypertensive efficacy; they have differing effects on renal plasma flow; and in a small pilot study of patients with congestive heart failure, the ARB demonstrated an apparent advantage in survival. Ongoing clinical trials will try to determine whether the effects of ARB can equal or even exceed the beneficial effects of ACE inhibitors on cardiovascular prognosis.

Angiotensin Receptor Antagonists↗
PubMed1997

Serum angiotensin-converting enzyme activity correlates positively with plasma angiotensin II: a population-based study of ambulatory blood pressure and the renin-angiotensin system.

A population-based study was performed in order to study the interrelationships of the circulating components of the renin-angiotensin system during basal conditions and their relations to blood pressure (BP), age and gender. One hundred and four women and 95 men, 16-70 years old, evenly age distributed and randomly selected from the population of Linköping, Sweden, participated. Venous blood was drawn at 08.00 hours and ambulatory BP recording was then performed. Serum angiotensin-converting enzyme (ACE) activity correlated with plasma angiotensin II (r = 0.20, P = 0.004), but when calculated separately according to gender, the correlation remained significant only in men (r = 0.33, P = 0.001). Plasma renin activity (PRA) correlated negatively with age (r = -0.30, P < 0.0001), but immunoreactive active renin (IRR) and angiotensin II did not. PRA and IRR correlated negatively with BP in women but correlations disappeared after age adjustment. The 23 women on oestrogen medication did not differ from the remaining 81 with respect to age (P = 0.5), IRR (P = 0.96) or angiotensin II (P = 0.4) levels, but PRA was higher (2.2 +/- 1.4 ng Ang l/ml/h and 1.5 +/- 0.9 ng Ang l/ml/h, respectively, P = 0.004). PRA (r = 0.38, P < 0.0001) and IRR (r = 0.49, P < 0.0001) correlated positively with the levels of angiotensin II. In conclusion the fact that PRA, but not IRR, declined with age and was higher among oestrogen-treated women, although angiotensin II was unaffected suggests IRR to be a more robust marker of angiotensin II levels than is PRA in a population-based setting. ACE correlates positively with angiotensin II in men.

Adolescent↗
PubMed1993

The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats. Effects of angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker.

BACKGROUND: The degree of cardiac hypertrophy is not only load dependent: Among other factors, the renin-angiotensin system may play a role in the regulation of cardiac myocyte growth. METHODS AND RESULTS: To evaluate the role of the renin-angiotensin system in volume overload-induced cardiac hypertrophy, we assessed: 1) the time course of changes in cardiac hemodynamics, cardiac anatomy, and plasma and cardiac renin activity in response to volume overload induced by two sizes of abdominal aortocaval shunt and 2) the effects of chronic treatment with an angiotensin converting enzyme inhibitor (ACEI) versus an angiotensin II receptor blocker on hemodynamics and cardiac hypertrophy. Drug treatment started 3 days before shunt surgery. An increase in left ventricular end-diastolic pressure (LVEDP) and the development of right ventricular (RV) and left ventricular (LV) eccentric hypertrophy in response to volume overload occurred within the first week after induction of the shunt. Plasma renin activity (PRA) and cardiac renin activity peaked shortly after induction of the shunt. During the chronic phase, LVEDP and PRA decreased somewhat but remained significantly elevated up to 7 weeks after shunt surgery. Cardiac renin activity returned toward normal within 4 weeks after surgery. Treatment with the ACEI enalapril caused only a modest decrease in LV internal diameter but did not affect increases in LV and RV weights in response to volume overload despite a major decrease in LVEDP after chronic treatment. In contrast, treatment with the angiotensin II receptor blocker losartan, which had similar effects on cardiac and peripheral hemodynamics, prevented dilation of the LV after 7 days and attenuated the dilation of the LV after 28 days. Moreover, increases in LV and RV weights were significantly attenuated by losartan. CONCLUSIONS: The development of volume overload-induced cardiac hypertrophy is associated with significant increases in PRA and cardiac renin activity shortly after induction of an aortocaval shunt. Whereas the two blockers of the renin-angiotensin system decreased LVEDP to a similar extent, only the angiotensin II receptor blocker blunted the hypertrophic response of the heart to volume overload, which is indicative for other than hemodynamic determinants of the cardiac hypertrophic response. One trophic factor may be cardiac angiotensin II generated via an angiotensin II-forming enzyme resistant to ACEI and possibly activated by cardiac volume overload.

Angiotensin II↗
PubMed1989

Angiotensin 'antipeptides': (-)messenger RNA complementary to human angiotensin II (+)messenger RNA encodes an angiotensin receptor antagonist.

(-)mRNA complementary to human angiotensin II (+)mRNA encodes the 'antipeptide' Glu-Gly-Val-Tyr-Val-His-Pro-Val which is structurally related to angiotensin II. Angiotensin II 'antipeptide' (antiANG II) and the desglutamyl heptapeptide (antiANG III) are Type I antagonists which inhibit the contractile action of angiotensin at smooth muscle receptors by binding to a negative modulatory site on the angiotensin receptor which is distinct from the angiotensin binding site. These findings may illustrate that the inhibitory binding site on the angiotensin receptor exists to accomodate a naturally occurring inhibitor(s), which is encoded by the DNA strand complementary to that encoding angiotensin II.

Amino Acid Sequence↗