Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Teprotide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1982

Angiotensin-converting enzyme inhibition in congestive heart failure: the concept.

Plasma renin activity frequently is increased in patients with congestive heart failure. This increase in inversely related to serum sodium concentration, but is not correlated with hemodynamic measurements. Nonetheless, inhibition of converting enzyme activity by administration of teprotide or captopril results in a decrease in systemic vascular resistance that is directly related to the control plasma renin activity. These data suggest that angiotensin II contributes to the systemic vasoconstriction of heart failure and that chronic inhibition of the renin-angiotensin system may have a salutary effect on left ventricular performance in patients with heart failure.

Angiotensin II↗
PubMed1982

Renal prostaglandin E2 biosynthesis: dependence on angiotensin II.

To study the interaction of the prohypertensive renin-angiotensin axis with the antihypertensive renal prostaglandins, angiotensin-converting enzyme inhibition (captopril and teprotide) and angiotensin blockade (Sar1-Ile8-AII) were produced in rabbits in vivo and renal slice prostaglandin E2 was measured in vitro after 30 minutes of incubation in Krebs-Ringer HCO3- buffer. In rabbits with angiotensin-converting enzyme inhibition, de novo prostaglandin E2 synthesis decreased in cortical, outer medullary and papillary slices by 85, 52 and 47 percent, respectively. Similar degrees of inhibition were observed with angiotensin blockade. It is concluded that renal prostaglandin E2 synthesis is angiotensin II dependent under these conditions. This finding suggests that any increase in the prohypertensive antinatriuretic renin-angiotensin axis may be associated with a secondary increase in renal prostaglandin E2 which may be acting in an antihypertensive natriuretic compensatory fashion.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1982

Effects of angiotensin-converting enzyme inhibitors on the vascular response to norepinephrine.

The effects of three types of angiotensin-converting enzyme inhibitor, SQ 14225 (captopril), SQ 20881 (teprotide) and SA 446 (Santen, Osaka, Japan), on the vascular contraction induced by norepinephrine were studied in the perfused rat mesenteric vascular bed. (1) SQ 14225 attenuated in the vascular contraction induced by norepinephrine, but SQ 20881 and SA 446 revealed no effect on vascular reactivity. (2) The effect of SQ 14225 was not altered in the presence of bradykinin or angiotensin II in the perfusate. On the basis of these results it is suggested that the attenuating effect on the vascular response to norepinephrine may be limited to SQ 14225 and that its effect is not mediated through the renin-angiotensin or kallikrein-kinin system.

3-Mercaptopropionic Acid↗
PubMed1988

Pharmacologic treatment of occlusive mesenteric ischemia in rats.

This study assessed the contribution of angiotensin II, oxygen-free radicals, and vasopressin to the mortality of acute mesenteric ischemia in rats. Rats received saline replacement (16 ml/kg/hr) for 3 hr during and after 85 min of superior mesenteric artery (SMA) occlusion. Only 21% of rats that received saline alone (n = 14, control) survived 48 hr, significantly less than the 100% survival of sham-operated rats (no SMA occlusion, n = 5, P less than 0.01). Neither teprotide (an angiotensin converting-enzyme inhibitor), allopurinol (to reduce oxygen-free radical formation), nor a specific vasopressin antagonist [1-(beta-mercapto-beta,beta-cyclopentamethyleneproprionic acid), 2-(O-methyl) tyrosine arginine-vasopressin] improved 48-hr survival, which was 17% in each group (n = 6, each). Survival improved significantly to 86% (n = 7, P less than 0.001) when intravenous glucagon (1.6 micrograms/kg/min) was given for 2 hr after SMA reperfusion. Survival after dopamine infusion (12 micrograms/kg/min iv) was 67% at 48 hr, a nearly significant improvement (n = 9, P less than 0.06). These results suggest that angiotensin II, oxygen-free radicals, and vasopressin do not contribute significantly to the high mortality observed after acute intestinal ischemia in this rat model, but that glucagon, and to a lesser extent, dopamine, are potentially therapeutic.

Allopurinol↗
PubMed1984

Effect of angiotensin II on RNA synthesis by isolated nuclei.

Peptide hormones are known to bind to cell surface receptors as the first step in the generation of their effects on target tissues. However, it remains uncertain whether internalized hormone might also play a role in the production of longterm or trophic effects of peptide hormones. Because the peptide hormone angiotensin II appears to be internalized by target cells, we studied the effect of this peptide on isolated hepatic nuclei. At both 5 X 10(-7)M and 5 X 10(-9)M, angiotensin II significantly increased RNA synthesis. This effect was not mimicked by Sar1-Ala8-angiotensin II (saralasin) or the unrelated nonapeptide teprotide.

Angiotensin II↗
PubMed1985

Captopril inhibits sodium and water transport in the toad skin, a model of the distal nephron.

Captopril (SQ 14225), an orally active angiotensin I-converting enzyme inhibitor (CEI), increases natriuresis and diuresis in man and experimental animals in vivo, as well as in the isolated perfused rat kidney, raising the possibility of a direct renal action of the drug. We tested this hypothesis by studying its effects in the isolated toad skin, a model of the distal nephron devoid of vascular and nervous influences. When added to the dermal bath, captopril caused a reversible, concentration-related decrease in short-circuit current (SCC), a measure of active transepithelial Na transport. Keeping the toads in 0.1 M NaCl for 4 or more days increased sensitivity to the drug, which then inhibited SCC maximally (49 +/- 12% at 3.4 X 10(-3) M, P less than 0.01, n = 10), suggesting its effect might be modulated by endogenous mineralocorticoid activity. Captopril also inhibited the increase in SCC and in osmotic water permeability caused by neurohypophyseal peptides (NHP). The increases in SCC by non-peptidic agents (nystatin, a polyene antibiotic, or norepinephrine, an adrenergic agonist) were not altered, ruling out a generalized toxic effect, or any significant inhibition of the Na pump by captopril. The apparently specific effect of the drug on the permeability responses to NHP seems to be exerted proximally to the apical border, since the response of the latter to other agents was preserved. The present data suggest SH groups may be involved, since other CEI lacking such groups (teprotide and MK-422) do not produce such effects. These observations support the notion that a direct tubular effect may be involved in the increased diuresis and natriuresis observed after administration of captopril.

Animals↗
PubMed1986

Angiotensin converting enzyme in the toad Bufo arenarum.

Angiotensin converting enzyme activity (ACEA) was determined in serum, kidney, whole skin and isolated epithelia homogenates of the South American toad Bufo arenarum. ACEA was present in the tissues and serum of the toad. The activity was higher in the kidney, as compared to that of the whole skin or isolated epithelium. Captopril, teprotide and EDTA, caused a significant decrease in the ACEA. Possible physiological roles for the presence of ACEA in the toad are discussed.

Animals↗
PubMed1987

Characterization of angiotensin I-converting enzyme activity in the freshwater turtle, Amyda japonica.

1. Angiotensin I-Converting Enzyme (ACE) activity has been characterized in the freshwater turtle, Amyda japonica. 2. Peak activity of ACE in plasma from the freshwater turtle was shown at pH 9.0, which was more alkaline compared to that of mammals. 3. Chloride requirements for the optimal ACE activity were different from species. 4. ACE inhibitors, EDTA, teprotide (SQ 20,881), Captopril (SQ 14,225) showed dose-dependent inhibitions of ACE activity in plasma from the freshwater turtle as well as mammals. 5. ACE activity was found in several different tissues with a different activity showing the highest activity in kidney homogenate from the freshwater turtle, Amyda japonica.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1981

Excitatory effect of converting enzyme inhibitors on efferent sympathetic postganglionic nerve activity to the kidney in the rat.

1. Experiments were designed to evaluate the effect of converting enzyme inhibitors on autonomic nervous system function in the rat. 2. Arterial blood pressure, heart rate, efferent postganglionic sympathetic activity and afferent nerve activity from the right renal nerves were recorded in anaesthetized, spontaneously breathing, non diuretic rats, either with an intact spinal cord or with a spinal cord transected at the T6 level, before, during and after intravenous injections of 0.5--1.0 mg/kg of teprotide or captopril. 3. After injection of drugs, efferent sympathetic nerve activity markedly increased and reached its peak value 4 min later, both in rats with an intact spinal cord (101 +/- 21% mean +/- SE, above the control discharge) and with a spinal cord transected at the T6 level (166 +/- 41%, above the control). 4. Afferent activity from the renal nerve, on the other hand, did not consistently change during converting enzyme blockade. 5. The results indicate that the efferent sympathetic excitation cannot be due either to a baroreceptor or to a renorenal reflex. This excitation might be responsible, at least in part, for the increase in renin secretion which follows the blockade of angiotensin-converting enzyme.

Adrenergic Fibers↗
PubMed1987

Effects of verapamil and converting enzyme inhibition on bilateral renal function of two-kidney, one-clip hypertensive rats.

Experiments were conducted in two-kidney, one-clip renal vascular hypertensive rats (GHR) to assess the responses of each kidney to acute treatment with the antihypertensive calcium channel blocking agent verapamil in the presence and in the absence of converting enzyme inhibitor (CEI). One group of GHR (0.2 mm inner diam. clip 3 weeks before study) were examined during a control period, and during a second period of infusion of verapamil (600 micrograms h-1 kg-1). A second group of GHR were examined during a control period, during CEI (teprotide, 3 mg h-1 kg-1) infusion and during a third period of verapamil (600 micrograms h-1 kg-1) infusion superimposed on CEI infusion. Although systemic blood pressure (BP) decreased from 175 +/- 4 to 149 +/- 5 mmHg (mean +/- SEM) in response to verapamil alone, renal blood flow for non-clipped kidneys increased from 5.9 +/- 0.4 to 6.5 +/- 0.3 ml/min, indicating a 30% reduction of renal vascular resistance (P values less than or equal to 0.01; n = 9). Glomerular filtration rate (GFR) for non-clipped kidneys (n = 24) increased from 0.91 +/- 0.09 to 1.47 +/- 0.14 ml/min and filtration fraction increased from 0.32 +/- 0.04 to 0.47 +/- 0.03 (P values less than or equal to 0.05). Urine flow rate and absolute and fractional sodium excretion for non-clipped kidneys increased. GFR for clipped kidneys decreased during verapamil. Treatment with CEI alone resulted in nearly identical responses of BP and function of the non-clipped kidney, except filtration fraction was unchanged. The addition of verapamil to ongoing converting enzyme blockade tended to augment the increased GFR of the non-clipped kidney. Plasma renin activity (PRA) increased from 30 +/- 3 to 59 +/- 7 ng of angiotensin (ANG) I h-1 ml-1 with verapamil alone, a significantly larger increment than the increase of PRA from 27 +/- 5 to 39 +/- 9 ng of ANG I h-1 ml-1 in GHR subjected to comparable blood pressure reduction by mechanical aortic constriction. Verapamil resulted in many similar effects on renal function to those observed during blockade of converting enzyme. The increased filtration fraction observed in response to verapamil may be the result of vasodilatation of the afferent arteriole or of an increase in the glomerular ultrafiltration coefficient.

Angiotensin II↗
PubMed1979

Increased glomerular filtration rate after converting-enzyme inhibition in essential hypertension.

To test the influence of an inhibitor of angiotensin-converting enzyme, teprotide (SQ 20881), we administered it to seven patients with essential hypertension and normal renal function and nine with an unequivocal reduction in creatinine clearance, caused by bilateral renal-artery stenosis in two and by essential hypertension in seven. Despite the fall in blood pressure (112.7 +/- 4.5 to 100.3 +/- 3.9 mm Hg, mean +/- S.E.M., P less than 0.01), there were prompt increases in both creatinine clearance (95.9 +/- 10.5 to 109.9 +/- 9.5 ml per minute per 1.73 m2 of body-surface area, P less than 0.01) and sodium excretion (17.0 +/- 5.9 to 31.7 +/- 7.2 mumol per minute, P less than 0.01) in patients with essential hypertension. The increase in glomerular filtration rate was most striking, averaging 33 per cent (66.0 +/- 10.3 to 88.0 +/- 9.2 ml per minute per 1.73 m2, P less than 0.001) in patients in whom an initial reduction was evident and hypertension was more severe. These observations suggest that a functional element, perhaps involving angiotensin-mediated renal vasoconstriction, frequently has a role in the reduction in glomerular filtration rate that occurs in essential hypertension. This class of agent may improve renal excretory function as it controls hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Role of vasopressin in experimental heart failure.

Neurohumoral vasoconstrictor systems are activated in heart failure and influence left ventricular function by modifying pre- and afterload. The renin-angiotensin system, sympathetic nerve activity and vasopressin have all been implicated as mechanisms of vasoconstriction. We investigated the vasoconstrictive action of vasopressin by blocking its vascular receptors by a specific antagonist in animal models of heart failure due to rapid right ventricular pacing in dogs and to aortocaval fistula, pulmonary stenosis and aortic stenosis in rats. In all animal models studied, we observed an inappropirately elevated secretion of vasopressin in association with a decreased plasma osmolality. We found only a small reduction of aortic pressure and peripheral vascular resistance following the vasopressin inhibitor. The renin-angiotensin system and sympathetic nerve activity were activated in all animal models. We injected teprotide in order to test the role of angiotensin in the regulation of peripheral vascular tone, and found a much greater decrease of blood pressure and peripheral vascular resistance than caused by the vasopressin antagonist. These experiments suggest that vasopressin and the renin system increase peripheral vascular tone in certain models of heart failure, and demonstrate a much greater importance for the renin system.

Animals↗
PubMed1985

Comparison of different drug interference with the renin-angiotensin system.

The hypotensive effects of inhibitors of renin or converting-enzyme (CE) were compared in normotensive sodium-depleted marmosets. Renin was inhibited by an antiserum or a monoclonal antibody against human kidney renin or by peptidic renin inhibitors. The fall in blood pressure after the administration of renin antibodies or inhibitors was accompanied by complete inhibition of plasma renin activity. Antiserum and monoclonal antibody induced a hypotensive response of similar magnitude as peptidic renin inhibitors but had a longer duration of action. Teprotide was used as a CE-inhibitor. Inhibition of renin or CE lowered blood pressure but did not affect heart rate. The magnitude of the hypotensive effect was comparable after renin- or CE-inhibition and depended on the pretreatment plasma renin activity. Inhibition of renin prevented the hypotensive response to inhibition of CE and vice versa. The results of these comparative studies suggest that, in states of sodium depletion, the acute hypotensive effects of renin- or CE-inhibitors are entirely due to their interference with the renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Vasoconstrictor role of vasopressin and angiotensin in experimental aortic stenosis in the rat.

The roles of vasopressin and angiotensin II in the regulation of peripheral vascular tone were investigated in control rats and in rats with chronic (15 weeks) aortic stenosis, by intravenous application of a specific antagonist to the vascular receptors of vasopressin and the angiotensin-converting enzyme inhibitor teprotide. The application of a Silver clip (0.6 mm) on the aorta ascendens produced a hemodynamically effective aortic stenosis with an increase in left ventricular weight (38%), a reduction in mean arterial pressure, cardiac index, and stroke volume index, and an increase in peripheral vascular resistance. In both groups of rats, a bolus injection of 30 micrograms of the vasopressin inhibitor d (CH2) 5 Tyr (Me) arginine vasopressin (AVP) showed an agonistic effect by increasing arterial pressure by 11 and 15 mm Hg, respectively, and no antagonistic effect in the control animals. In the rats with chronic aortic stenosis we observed a significant fall in blood pressure (4.1 +/- 5.5 mm Hg; p less than 0.05) and a reduction in peripheral vascular resistance of 6.3% (p less than 0.02). Stroke volume index and heart rate did not change. Most of the animals with aortic stenosis had inappropriately elevated plasma levels of vasopressin and increased levels of plasma renin concentration. The rats with aortic stenosis and inappropriately increased values of vasopressin showed significantly lower plasma osmolality, cardiac index, and stroke volume index and increased peripheral vascular resistance compared with the stenosed rats with a normal osmoregulation of vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1984

Role of angiotensin II, alpha-adrenergic system, and arginine vasopressin on arterial pressure in rat.

Three pressor systems regulate arterial pressure (MAP): angiotensin II (ANG II), the alpha-adrenergic system, and arginine vasopressin (AVP). In this study we determined the ability of each system to support MAP in the conscious rat when the other two systems were inactivated. After administration of the converting-enzyme inhibitor teprotide (CEI) and the alpha-adrenergic receptor antagonist phenoxybenzamine (POB), MAP decreased 40% as a result of a 45% decrease in peripheral vascular resistance (PVR). Despite hypotension, plasma AVP levels were not increased, and an AVP pressor antagonist (AVP-A) did not result in a further decrease in MAP. Thus the profound hypotension after POB plus CEI was the result of inhibition of all three systems. POB, rather than CEI, prevented AVP release since following hypotensive hemorrhage, plasma levels reached 51 +/- 13 pg/ml with CEI but only 4.7 +/- 0.8 pg/ml with POB. To study the pressor effect of AVP alone, AVP was infused in POB plus CEI-treated rats. AVP increased MAP (from 68 +/- 4 to 92 +/- 5 mmHg; P less than 0.005) and plasma AVP (to 13.8 +/- 1.9 pg/ml). Since POB inhibited both the AVP and the alpha-adrenergic system, the role of ANG II alone was determined in POB-treated rats. In the presence of ANG II MAP was 97 +/- 1 mmHg. To study the alpha-adrenergic system, MAP was determined in CEI plus AVP-A-treated rats. In the presence of an intact alpha-adrenergic system MAP was 101 +/- 1 mmHg. We conclude that PVR and MAP are profoundly decreased in the absence of all three pressor systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1988

Cardiovascular effects of AVP and ANG in experimental pulmonic stenosis in rats.

Our objectives were to examine the role of vasopressin and renin in the regulation of peripheral vascular tone in an animal model of right ventricular failure due to chronic (10 wk) pulmonic stenosis. We tested in chronically instrumented conscious control rats and in rats with pulmonic stenosis on a normal and a high-sodium diet both vasoconstrictor systems by applying specific inhibitors. The rats with pulmonic stenosis showed significant hemodynamic changes, a hypertrophy of the right ventricle, increased levels of plasma renin concentration, and inappropriately elevated plasma levels of vasopressin in comparison to control animals. Plasma renin concentration was suppressed in the sodium-loaded controls. After the administration of a specific inhibitor of the vascular receptors of arginine vasopressin [30 micrograms, d(CH2)5Tyr(Me)AVP], we found no hemodynamic changes in control rats on the normal diet, a reduction of mean arterial pressure in the sodium-loaded controls (4 +/- 4 mmHg; P less than 0.005), and in the animals with pulmonic stenosis and normal sodium intake (5 +/- 5 mmHg; P less than 0.001) and high-salt diet (6 +/- 7 mmHg; P less than 0.02). Intravenous bolus injection of teprotide (1 mg/kg) resulted in a decrease of mean arterial pressure in the control group (normal diet) of 9 +/- 8 mmHg (P less than 0.005). The fall of blood pressure (22 +/- 10 mmHg; P less than 0.001) in the rats with pulmonic stenosis was significantly greater (P less than 0.01) and was strongly related to plasma renin concentration. Therefore, vasopressin and the renin-angiotensin system contribute to an increase of peripheral vascular tone in chronic pulmonic stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1990

Combined intrarenal blockade of the renin-angiotensin system in the conscious dog.

We produced maximal or near-maximal acute intrarenal blockade of the renin-angiotensin system (RAS) by combining inhibitors. Intrarenal infusion of the renin inhibitor, ACRIP, the converting enzyme inhibitor, teprotide, and saralasin were administered individually or combined in random order. The inhibitors were infused for 20 min in doses that did not produce systemic effects in uninephrectomized conscious dogs in sodium balance at 10 meq/day. Significant increases in urine flow rate (UV; F = 97, P less than 0.0001), urinary sodium excretion (UNaV; F = 220, P less than 0.0001), glomerular filtration rate (GFR; F = 64, P less than 0.0001), and renal plasma flow (RPF; F = 108, P less than 0.0001) were observed with each blocker, whether alone or in combination except that ACRIP alone did not alter GFR or RPF. The increase in renal function was related to the number of blockers (3 greater than 2 greater than 1). With the three blockers combined UV increased approximately sixfold (from 0.5 +/- 0.06 to 2.9 +/- 0.03 ml/min), UNaV approximately 10-fold (from 3 +/- 0.4 to 34 +/- 2.8 mueq/min), GFR from 31 +/- 2 to 49 +/- 2 ml/min, RPF from 59 +/- 1 to 120 +/- 4 ml/min, and fractional excretion of sodium from 0.06 +/- 0.01 to 0.5 +/- 0.4% (all P less than 0.001). These changes did not occur where the inhibitors were infused systemically and the changes during intrarenal blocker administration were blocked completely with co-administration of angiotensin II intrarenally. The intrarenal RAS is a potent physiological regulator of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMedDate not supplied

Differences in response to the peptidyldipeptide hydrolase inhibitors SQ 20,881 and SQ 14,225 in normal-renin essential hypertension.

We compared vascular and hormonal responses to teprotide (SQ 20,881) and captopril (SQ 14,225) in patients with normal renin essential hypertension given a 10 mEq sodium diet. In 10 patients receiving SQ 20,881, significant changes occurred in diastolic blood pressure (DBP, -13 +/- 2.5 mm Hg), angiotensin II (-7.1 +/- 2.1 pg/ml), and plasma renin activity (PRA, +6.6 +/- 1.9 ng/ml/hr) (p < 0.01 in all cases). Twenty-one patients receiving SQ 14,225 had significant changes in mean DBP (-18 +/- 1.5 mm Hg), angiotensin II (-6.6 +/- 1.5 pg/ml), and PRA (+7.8 +/- 2.4 ng/ml/hr) (all p values < 0.01). In spite of a significantly greater hypotensive response (p < 0.02), patients receiving SQ 14,225 showed increments in PRA and decrements in angiotensin II that did not differ significantly from those seen after SQ 20,881. Moreover, there was a significant change in plasma kinins in patients receiving SQ 20,881 (+2.0 +/- 0.9 ng/ml, p < 0.01) but no change in kinins in patients receiving SQ 14,225 (0.0 +/- 0.1, ns). We conclude that there are important differences in the mechanism mediating the hypotensive response to SQ 20,881 and SQ 14,225 in normal renin essential hypertension.

Adult↗