Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to determine the pharmacologic effects of rat atrial natriuretic factor (r-ANF; 250 ng/kg/min), endothelin-3 (ET-3; 340 ng/kg/min), and combined r-ANF and ET-3 infusion on cardiac hemodynamics and renal function in anesthetized rats. The change in mean arterial pressure (delta MAP) was 13 +/- 2 mm Hg during ET-3 infusion alone. Delta MAP was -9 +/- 2 mm Hg during r-ANF infusion alone. Combined infusion of ET-3 and r-ANF resulted in a change in MAP of -7 +/- 3 mm Hg. The decrease in MAP during combined infusion of ET-3 and r-ANF occurred due to a decrease in cardiac output. Infusion of r-ANF did not block the cardiac output. Infusion of r-ANF did not block the ET-3-induced increase in total peripheral resistance (TPR). Infusion of r-ANF alone resulted in an 11-fold increase in urinary sodium excretion. ET-3 infusion completely blocked the ANF-induced natriuresis in part by markedly decreasing the glomerular filtration rate (GFR). ET-3 or r-ANF infusion alone resulted in two- or eightfold increases, respectively, in circulating r-ANF levels compared to vehicle alone. However, combined infusion of r-ANF and ET-3 resulted in a dramatic 27-fold increase in circulating r-ANF when compared to levels obtained during vehicle infusion alone. The present study demonstrates that at pharmacologic levels, r-ANF blocks the pressor action of ET-3 by decreasing cardiac output rather than TPR. Furthermore, ET-3 blocks the natriuretic action of r-ANF, partly by decreasing GFR.
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PMID:Atrial natriuretic factor blocks the pressor action of endothelin. 170 77

1. The effects of the ETA receptor antagonist, BQ-123 on blood pressure changes induced by various members of the endothelin (ET)/sarafotoxin (SX) peptide superfamily were investigated in the anaesthetized rat. 2. ET-1 (1 nmol kg-1, i.v. bolus) induced a sustained increase in mean arterial pressure (MAP, maximum increase 44 +/- 3 mmHg). Intravenous injection of BQ-123 at 0.2, 1.0 or 5.0 mg kg-1 5 min before ET-1 inhibited the pressor response by 18, 50 and 61%, respectively. The ET-1 pressor response was inhibited by 75% when the peptide was given 60 min after the start of a 120 min i.v. infusion of BQ-123 (0.2 mg kg-1 min-1). 3. In addition to ET-1, BQ-123 (1 mg kg-1, i.v. bolus) attenuated the pressor responses to big ET-1 (1 nmol kg-1, i.v., bolus, maximum increase in MAP: 68 +/- 7 mmHg), ET-3 (3 nmol kg-1, i.v., bolus, maximum response: 30 +/- 3 mmHg), SX6b (1 nmol kg-1, i.v., bolus, maximum response: 41 +/- 5 mmHg) and SX6c (1 nmol kg-1, i.v., bolus, maximum response: 24 +/- 4 mmHg) by 65, 60, 88 and 50%, respectively. 4. With the exception of big ET-1, all the peptides used in this study induced an initial transient depressor response (-32 +/- 3 mmHg, n = 18). Although BQ-123 (1 mg kg-1, i.v., bolus) did not affect the absolute magnitude of the fall in MAP, the ETA receptor antagonist significantly prolonged the depressor responses induced by ET-3 and SX6b. 5. Thus, BQ-123 attenuates the pressor, but not the depressor effects of ET-1, big ET-1, ET-3, SX6b and SX6c. Complete inhibition of the pressor responses could not be achieved, suggesting that a component of the pressor response is not mediated via the ETA receptor.
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PMID:Incomplete inhibition of the pressor effects of endothelin-1 and related peptides in the anaesthetized rat with BQ-123 provides evidence for more than one vasoconstrictor receptor. 844 3

Renal nephron segments are heterogeneous, and receptors for endothelin (ET)-1, ET-3, Angiotensin II (AII), epidermal growth factor (EGF), and insulin-like growth factor I distribute differently along the nephron segments. Recently, growth factors and vasoactive substances are reported to stimulate mitogen-activated protein kinase (MAP-K). In this study, we showed that mRNA and proteins of MEK-K, Raf-1-K, MAPK-K, MAP-K (p42 and p44), and S6-K are expressed ubiquitously in intact nephron segment. We demonstrated that four tiers of a cascade composed of the Raf-1-K, MAP-K, MAP-K, and S6-K are stimulated by ET-1 and ET-3 in rat intact glomeruli (Glm) via primarily B-type ET receptors and PKC. The stimulatory effect of EGF and IGF-I to MAP-K activity is inhibited by a tyrosine kinase inhibitor in Glm. IGF-I significantly stimulates MAP-K activity and EGF and All moderately stimulate MAP-K activity in the proximal convoluted tubule (PCT). EGF significantly increased MAP-K cascades and ET-1 and ET-3 slightly increased MAP-K cascades in the medullary thick ascending limb (MTAL). EGF significantly stimulated MAP-K cascades, and ET-1 and ET-3 moderately stimulate MAP-K cascades in the outer medullary collecting duct (OMCD) and the inner medullary collecting duct (IMCD). MAPK-K and S6-K are similarly stimulated by these agonists in each segment. This study shows that MAP-K cascades are expressed in every nephron segment. ET-1, ET-3, All, EGF, and IGF-I stimulate MAP-K cascades heterogeneously along the nephron segment. It was concluded that MAP-K cascades play an important role in the regulation of renal function.
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PMID:Presence and regulation of Raf-1-K (Kinase), MAPK-K, MAP-K, and S6-K in rat nephron segments. 874 82