Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacological blockade of the renin-angiotensin converting enzyme reportedly alters the heart rate (HR) power spectrum in conscious dogs, suggesting that these hormones contribute to the short-term regulation of arterial blood pressure. We tested this possibility using four independent procedures. First, HR power spectrum was determined in seven awake dogs before and after administration of enalaprilat (300 ng/kg), a converting-enzyme inhibitor. There were no significant changes in the average amplitude for the spectral peak between 0.003 and 0.1 Hz (i.e., the "low-frequency peak"). Second, the HR power spectrum was measured in 11 awake rabbits before and after treatment with deoxycorticosterone acetate (1 mg.kg-1.day-1) and salt (0.9% saline ad libitum) for 7 days to depress plasma renin levels. There were no significant changes in the amplitude of the HR power spectrum, although mean HR decreased from 206 +/- 3 to 184 +/- 4 beats/min after treatment. In the third experiment, another group of rabbits (n = 8) was tested after 2 wk on a low-salt diet to elevate plasma angiotensin levels and then after 2 wk on a normal salt diet. Once again there were no significant effects on the HR power spectrum. Finally, tranquilized dogs (n = 9) were subjected to sinusoidally varying lower body negative pressure at selected frequencies of 0.008-0.12 Hz. Tests were conducted in the control state and after administration of an angiotensin receptor antagonist (saralasin, 1 microgram.kg-1.min-1). Lower body negative pressure-induced fluctuations in arterial blood pressure were similar in both states. We find no evidence for the role of the renin-angiotensin system in the moment-to-moment regulation of arterial pressure and HR.
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PMID:Angiotensin II does not contribute to rapid reflex control of arterial pressure. 187 3

1. We previously found that kidneys isolated from salt-restricted rats were refractory to atrial natriuretic peptide compared with kidneys from salt-loaded rats. Because the intrarenal tissue renin-angiotensin system may modulate renal responses to atrial natriuretic peptide, we examined the effect of dietary NaCl loading on the responses of isolated perfused kidneys from normal rats to atrial natriuretic peptide, before and after the addition of angiotensin II receptor antagonists or angiotensin I converting enzyme inhibitors to the perfusate. 2. Atrial natriuretic peptide increased the glomerular filtration rate and sodium excretion of kidneys from NaCl-loaded rats. The addition of angiotensin receptor antagonists or converting enzyme inhibitors partially reversed the increments in glomerular filtration rate but not the increments in sodium excretion, leading to an increased fractional sodium excretion. In the absence of atrial natriuretic peptide, these agents did not affect glomerular filtration or sodium excretion. Kidneys from NaCl-restricted rats did not respond to atrial natriuretic peptide or to the inhibitors and antagonists, either separately or in combination. 3. After NaCl loading, the intrarenal renin-angiotensin system may augment the glomerular response to atrial natriuretic peptide while simultaneously inhibiting the natriuretic response to atrial natriuretic peptide. However, activation of the intrarenal renin-angiotensin system is not responsible for the refractoriness of kidneys from salt-restricted rats to atrial natriuretic peptide.
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PMID:Intrarenal angiotensin II inhibition influences the actions of atrial natriuretic peptide. 216 73

1. Changes in tension in response to cumulative additions of angiotensins (i.e., angiotensinogen, angiotensin I and angiotensin II), bradykinin and acetylcholine were monitored isometrically on ring preparations from porcine interlobar renal arteries. 2. Angiotensins consistently elicited contractile responses, whereas both bradykinin and acetylcholine produced relaxation of the arterial rings when active tone was induced by prostaglandin F2 alpha. 3. Contractile responses to angiotensin II could be completely blocked by the combined action of the cyclo-oxygenase inhibitor, indomethacin (1 microM) and the lipoxygenase inhibitor, nordihydroguairetic acid (NDGA, 10 microM). 4. Relaxant responses to bradykinin were unchanged during blockade of thromboxane A2 synthesis by dazoxiben (30 microM) and proved to be largely resistant to blockade by indomethacin (1 microM) and the prostaglandin I2 (prostacyclin) synthesis inhibitor, tranylcypromine (40 microM). 5. The angiotensin receptor blocker, saralasin (10 and 100 nM) antagonized responses to angiotensinogen, angiotensin I and angiotensin II effectively and with similar potency. Enalaprilic acid, the active metabolite of the converting enzyme inhibitor enalapril (300 nM), attenuated responses to angiotensin I but failed to inhibit those to angiotensinogen up to 1 microM. The serine protease kallikrein (0.001 to 1 mu ml-1) produced a dose-dependent shift to the left of the concentration-response curve for angiotensinogen. 6. It is suggested that the porcine interlobar renal artery possesses a local renin-angiotensin system with activatable angiotensin II forming enzyme(s) within the vessel wall.
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PMID:Pharmacological evidence for the existence of a local renin-angiotensin system in porcine interlobar renal arteries. 228 72

Spirally cut strips of human saphenous vein and pulmonary artery preincubated with 3H-noradrenaline were superfused in the presence of corticosterone and desipramine or cocaine. In the saphenous vein angiotensin I, angiotensin II and angiotensin III concentration-dependently increased the electrically (2 Hz) evoked tritium overflow (relative order of potency: angiotensin II greater than angiotensin I greater than angiotensin III). The angiotensin receptor antagonist saralasin displaced the concentration-response curve of angiotensin II to the right, and also blocked the facilitatory effect of angiotensin III. Captopril, an inhibitor of angiotensin converting enzyme, did not modify the concentration-response curve of angiotensin I and did not significantly diminish the release-increasing effect of the nonselective beta-adrenoceptor agonist isoprenaline, whereas saralasin attenuated the facilitatory effect of the beta 2-adrenoceptor agonist procaterol. In the pulmonary artery the angiotensin receptor agonist Val5-angiotensin II-Asp1-beta-amide also increased the electrically evoked tritium overflow in a concentration-dependent manner. It is concluded that the sympathetic nerve fibres of the human saphenous vein (and probably of the human pulmonary artery as well) are endowed with facilitatory presynaptic angiotensin receptors. Angiotensin I exerted its facilitatory effect in the saphenous vein probably via direct stimulation of angiotensin receptors but not by conversion to angiotensin II. Furthermore, the beta 2-adrenoceptor-induced facilitation of noradrenaline release may in part be mediated by local stimulation of angiotensin II synthesis, which may occur by increased formation or activation of renin and/or increased availability of angiotensinogen.
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PMID:Facilitatory presynaptic angiotensin receptors on the sympathetic nerves of the human saphenous vein and pulmonary artery. Potential involvement in beta-adrenoceptor-mediated facilitation of noradrenaline release. 284 3

Angiotensin II, the biologically active component of the renin-angiotensin system, acts throughout the body to produce an impressive number of cardiovascular, endocrine, metabolic, and behavioral effects. Major actions include elevation of arterial pressure, stimulation of aldosterone secretion, and a variety of effects on the kidneys, brain, and pituitary. Investigation of the role of the renin-angiotensin system in physiological regulation has been greatly facilitated by the availability of specific inhibitors of the formation or actions of angiotensin II, most notably converting-enzyme inhibitors and angiotensin receptor antagonists. Studies with these agents have clearly shown that the renin-angiotensin system plays an important role in the defense of body balance and blood pressure in hypovolemic state, including sodium deficiency and hemorrhage. The inhibitors also lower blood pressure in some forms of hypertension, and converting-enzyme inhibitors are proving to be effective antihypertensive agents.
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PMID:The renin-angiotensin system and body function. 299 6

The specific angiotensin receptor antagonist, Sar1, Thr8AII (sarthran), was infused intracerebroventricularly in alert spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive rat strains. This resulted in a mean decrease of 35 mm Hg in the SHR group by 25 min post-infusion, and corresponding decreases in the WKY and SD rats of 13 and 15 mm Hg, respectively. A prominent transient sarthran-induced elevation in blood pressure was noted in the SHR group during the 5-min infusion. This agonistic effect was not observed in members of the WKY and SD strains. These data encourage the use of sarthran as a valuable pharmacological probe in the examination of the role of the brain renin-angiotensin system in hypertension.
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PMID:Central effects of a specific angiotensin receptor antagonist, sarthran (Sar1, Thr8AII) in normotensive and spontaneously hypertensive rat strains. 337 58

The angiotensin receptor is the only macromolecular component of the renin-angiotensin system which has not yet been purified and characterized in the isolated state. A purified preparation could be useful for identifying the amino acid residues it preferentially recognizes in various positions of defined peptide ligands, and for elucidating the proximate molecular mechanism by which the binding event is transduced into a cellular response. Such knowledge should expedite the development of receptor antagonists which might be more physiologically specific than other inhibitors of the system. This paper elaborates on these thoughts, and describes some recent progress in purification of the rabbit hepatic receptor.
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PMID:Thoughts and studies on purification of the angiotensin II receptor. 353 80

1. Administration of captopril (1.5 mg/kg i.v.) to anaesthetized dogs was associated with an increase in renal blood flow of 56 ml min-1 (s.e.m. = 13, n = 9) despite a significant fall of 17 mmHg (s.e.m. = 5, n = 9) in mean arterial pressure. 2. Treatment of dogs with the angiotensin receptor antagonist, Sar1 Ile8-angiotensin II (2.5 micrograms/kg per min i.v.), or the cyclo-oxygenase inhibitor indomethacin (10 mg/kg i.v.) did not prevent the renal vasodilation and hypotension following angiotensin-converting enzyme inhibition. This suggests that these effects are neither solely due to inhibition of the renin-angiotensin system nor mediated by prostaglandins. 3. Increased urinary kinin excretion, possibly reflecting increased renal concentrations of kinins, accompanied the renal vasodilation after both captopril and renal artery occlusion. 4. The kallikrein-kinin system may play a role in the regulation of the renal vasculature in anaesthetized dogs.
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PMID:Role of the kallikrein-kinin system in the renal effects of angiotensin-converting enzyme inhibition in anaesthetized dogs. 627 63

The renin-angiotensin system has been shown to participate in the pathophysiology of chronic heart failure in many patients. However, the immediate assessment of this contribution in individual patients may sometimes be difficult. As a pharmacologic estimate of angiotensin II receptor activity, we infused the angiotensin II analogue, saralasin, in 20 patients with severe chronic congestive heart failure (CHF). The infusion resulted in blood pressure responses ranging from an agonist pressor response (increased systemic resistance) in patients with low intrinsic renin-angiotensin system activity, to an antagonist depressor response (decreased systemic resistance) in patients with marked activation of the renin-angiotensin system. The ability of the saralasin response to pharmacologically estimate angiotensin II receptor activity in CHF was further revealed by two physiologic maneuvers that decrease endogenous circulating angiotensin II and angiotensin II receptor occupancy. Both converting enzyme inhibition with captopril and sodium repletion, factors known to decrease endogenous angiotensin II activity, provoked agonist responses to saralasin infusion. Furthermore, saralasin was able to reverse the orthostatic hypotension precipitated by converting enzyme inhibition of angiotensin-dependent vascular tone. In summary, saralasin provided a means to estimate angiotensin receptor activity and may therefore serve as a probe of angiotensin-mediated vasoconstriction in the pathophysiology of chronic CHF.
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PMID:Estimation of angiotensin II receptor activity in chronic congestive heart failure. 632 65

Multiple lines of evidence support the existence of a vascular renin-angiotensin system independent of the circulating system. Vascular renin appears to originate from both uptake of plasma renin and in situ synthesis. Renin may bind to vascular endothelium. In addition, the endothelium is capable of activating inactive renin. Cell-surface-bound renin and angiotensin-converting enzyme constitute a biochemical cascade on the endothelial surface, resulting in a high local concentration of angiotensin. The role of the intracellular system is unclear. Intracellular angiotensin may regulate the angiotensin receptor and modulate the vascular response to exogenous angiotensins. Recent data also suggest that neutrophils and platelets provide mobile pathways by which cell-bound or released enzymes can activate and amplify the renin-angiotensin biochemical cascade. The mobile angiotensin pathways may be important in the inflammatory vascular response, edema formation, and vasospasm of vascular injury. Taken together, the vascular wall renin-angiotensin system may play an important role in cardiovascular homeostasis. We postulate that abnormalities in the control of this system may result in local vasospasm or systemic hypertension.
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PMID:Vascular wall renin-angiotensin pathway in control of the circulation. A hypothesis. 638 99


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