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

The antihypertensive effect of clonidine has been attributed to acute inhibition of sympathetic outflow from the central nervous system. This conclusion is derived from experiments with single doses of clonidine. The mechanism of the long-term blood pressure-lowering effect of clonidine has been less well characterized. Antihypertensive therapy may alter renal hemodynamics and these changes may ultimately affect systemic blood pressure. We studied the effect of long-term clonidine therapy on intrarenal hemodynamics, the renin-angiotensin system, and selected indices of sympathetic nervous system activity in 13 patients with essential hypertension to further elucidate its action. Long-term clonidine therapy resulted in decreased MAP and RVR associated with the suppression of supine but not upright PRA. RPF, RBF, FF, and WBV did not change. UKA, on index of the the putative vasodilating renal kallikrein-kinin system, was also not changed. Our findings suggest a role for PRA in modulating RVR during long-term clonidine therapy. This was associated with the reduction observed in MAP.
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PMID:Reduced renovascular resistance by clonidine. 49 99

We evaluated the effect of acute unilateral renal denervation (DNX) on the tubuloglomerular feedback (TGF) mechanism in Inactin-anesthetized hydropenic male 8- to 10-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). SHR had higher mean arterial pressure (MAP, 28%) and renal vascular resistance (RVR, 35%), whereas renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and sodium excretion were similar. DNX in SHR did not change MAP but decreased RVR (26%) and increased RBF (29%), GFR (16%), urine flow (52%), and sodium excretion (431%). DNX did not affect these in WKY. Loop of Henle perfusion with Ringer solution reduced early proximal flow rate (EPFR) in SHR more than in WKY; significantly different at a loop flow of 20 nl/min (9.8 +/- 0.7 vs. 6.5 +/- 0.7 nl/min). DNX in SHR increased the nonperfused EPFR from 25.6 +/- 1.1 to 31.7 +/- 1.3 nl/min and reduced TGF responses during perfusion at both 20 nl/min (9.8 +/- 0.7 vs. 4.4 +/- 0.7 nl/min) and 40 nl/min (14.2 +/- 1.1 vs. 10.4 +/- 0.7 nl/min). TGF sensitivity was attenuated by DNX, as indicated by reduced maximum reactivity (-0.89 +/- 0.14 to -0.36 +/- 0.07) and increased turning point (16.5 +/- 0.9 to 25.2 +/- 2.9 nl/min). TGF responses in WKY were not influenced by DNX. Sham denervation did not alter renal hemodynamics and TGF. These results indicate that renal nerves exert a tonic influence on the renal vasculature and the TGF system in SHR but not in WKY. Enhanced TGF responsiveness may be involved in volume retention and in the maintenance of hypertension in SHR.
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PMID:Attenuation of enhanced tubuloglomerular feedback activity in SHR by renal denervation. 233 Sep 89

The effect of the rate of infusion of single and multiple doses of cyclosporine (CsA) on renal function was evaluated in Sprague-Dawley rats. CsA was dissolved in cremophore (Crem) or Tween 80 (Tween) and infused over consecutive 10-min periods at doses of 10, 20, 30 and 40 mg/kg. CsA-Crem and CsA-Tween produced similar and progressive changes in MAP, RBF, and RVR. By the end of the infusion, the mean values (% of control) of MAP (122 +/- 16% and 131 +/- 22%), RBF (56 +/- 11% and 66 +/- 20%), and RVR (222 +/- 38% and 232 +/- 134%) were significantly different from their respective preinfusion values. Infusion of Crem alone resulted in renal vasodilation at low doses and renal vasoconstriction at high doses. Vasoconstriction was not produced by infusion of Tween alone. In addition, animals were treated with vehicle alone (Gp 1), CsA 10 mg/kg/day by injection (Gp 2), or CsA 20 mg/kg/day by i.v. infusion over 4 hr (Gp 3), and were studied at 1 week. Systemic toxicity was greater with the 4-hr infusion as judged by an increase in MAP. The mean values of MAP were 107 +/- 8 (Gp 1), 101 +/- 13 (Gp 2), and 135 +/- 5 mm Hg (Gp 3; p less than 0.05). However, renal function was less severely affected with the 4-hr infusion. The mean values of CIn were 434 +/- 99 (Gp 1), 298 +/- 101 (Gp 2; p less than 0.05), and 425 +/- 114 microL/min/100 g BW (Gp 3); and the mean values for RBF were 2.72 +/- 0.74 (Gp 1), 2.08 +/- 0.17 (Gp 2; p less than 0.05), and 3.35 +/- 0.61 mL/min/100 g BW (Gp 3), respectively. Microangiograms showed marked abnormalities in the intrarenal perfusion pattern in the rats injected with CsA, 10 mg/kg BW. In rats infused over 4 hr with CsA, 20 mg/kg BW, the microangiographic pattern was normal. These studies demonstrate that the acute hemodynamic effects of CsA are directly related to the rate of infusion. Furthermore, the renal toxicity which follows repetitive injection of CsA can be minimized or avoided by administering CsA as a slow infusion. In addition to the total dose administered, the rate of infusion is an important determinant of nephrotoxicity.
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PMID:Influence of the rate of infusion on cyclosporine nephrotoxicity in the rat. 277 85

Chronically catheterized fetal lambs (n = 11, gestational age 111-139 days) and neonatal lambs (n = 20, postnatal age 4-30 days) were studied to explore during development the relationship of renal hemodynamic responses during hypoxemia to plasma epinephrine concentration (E), plasma norepinephrine concentration (NE), plasma arginine vasopressin concentration (AVP), and plasma renin activity (PRA). A low oxygen gas mixture (11.1 +/- 0.1% O2) was administered for 30 min to the pregnant ewe or neonatal lamb to induce hypoxemia with maintenance of normal arterial pCO2 and pH. Arterial blood pressure was recorded continuously and renal blood flow (RBF) was determined by the radiolabeled microsphere technique. Moderate hypoxemia (pO2 16 +/- 2 torr and 33 +/- 6 torr in fetus and neonate, respectively) induced increases in E, NE (measured by radioenzymatic assay), and AVP (measured by radioimmunoassay) in both fetus and neonate. PRA (measured by radioimmunoassay) also increased in response to hypoxemia in neonatal lambs. The change in mean arterial pressure with hypoxemia (delta MAP) was significant in fetuses (delta MAP 8 +/- 14%, p less than 0.05) but not in lambs (delta MAP 1 +/- 10%, p greater than 0.5). Similarly, the change in renal blood flow with hypoxemia (delta RBF) was significant (delta RBF -51 +/- 24%, p less than 0.001) in fetuses but not in neonatal lambs (delta RBF -9 +/- 38%, p greater than 0.1). These results reflected a change in renal vascular resistance with hypoxemia (delta RVR) that was significant in fetal lambs (delta RVR 169 +/- 168%, p less than 0.01) but not in neonatal lambs (delta RVR 51 +/- 180%, p greater than 0.2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal hemodynamic responses to hypoxemia during development: relationships to circulating vasoactive substances. 328 Nov 20

Infusion of prostacyclin (PGI2) reportedly attenuates renal ischemic injury in the dog and the rat. In the dog, PGI2 is a potent renal vasodilator; in the rat a direct action on the renal vasculature is not always apparent. To determine whether or not the protective effect of PGI2 on postischemic ARF was hemodynamically mediated, studies were performed in uninephrectomized Sprague-Dawley rats before and after a 40 minute period of complete renal artery occlusion. In response to the preischemic infusion of PGI2 for 30 minutes at 160 ng/kg body wt/min i.v. (N = 7), MAP and RBF fell to 86 +/- 7% (P less than 0.0001) and 84 +/- 9% (P less than 0.05) of baseline values, respectively. RVR initially declined to 81 +/- 9% of baseline values (P less than 0.025) but returned to 102 +/- 13% of baseline values prior to the period of ischemia. Following the period of ischemia, reflow of blood in the rats receiving PGI2 was delayed when compared to rats not receiving PGI2 (N = 7). RBF returned to only 76 +/- 19% of the initial values in PGI2-treated rats (P less than 0.01) but to 90 +/- 12% of the initial values in rats receiving buffer alone (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effect of prostacyclin on postischemic acute renal failure in the rat. 332 94

The mechanism for the renal hemodynamic and tubular action of furosemide (F) was investigated in nine anesthetized dogs. F was administered intrarenally at 50 micrograms/ml/min in isotonic saline with and without the addition of indomethacin (I) at 36 micrograms/ml/min and PGE1 at 2 micrograms/ml/min in isotonic saline. F increased the ERPF, RBF, UV, Cosm, CH20, UNaV and UKV from the experimental kidney and UV, Cosm, CH20, UNaV and UKV from the control kidney. It decreased the RVR of the experimental kidney and had no effect on GFR and MAP. I administration alone produced effects opposite to those of F. The addition of F to I reversed the renal hemodynamic effects of I but partly its tubular effects. The addition of PGE1 to I + F infusion further increased the fractional excretion of free water by both kidneys but had not other effects. The results of the present investigation suggest that the renal hemodynamic effects of F ar not mediated through the action of prostaglandins but rather due to a direct vascular effect of the drug. On the other hand, its tubular actions are mediated through prostaglandins.
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PMID:The mechanism for the renal hemodynamic and tubular action of furosemide. 722 27

Since dietary salt loading enhances nitric oxide (NO) generation in the kidney, we investigated the hypothesis that changes in salt intake have specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR) in anesthetized rats during intravenous infusions of graded doses of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats were maintained on a high salt (HS) or low salt (LS) diet for two weeks. Compared to those on LS, rats on HS had a greater increase in mean arterial pressure (delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RVR (+160 +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (delta RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes in HQVR were similar in the two groups. The enhanced RVR response to L-NAME in HS rats could not be ascribed to the higher renal perfusion pressure (RPP) since it persisted in rats whose RPP was controlled by adjustment of a suprarenal aortic clamp. Changes in RVR with an NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin activity in both HS and LS rats. After inhibition of ACE with captopril, or of angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L-NAME remained greater in HS than LS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt. 752 72

The renal effects of low-dose cyclosporin A (CsA) treatment in severe psoriasis was investigated in 10 patients treated with a mean CsA dose of 3.23 (range 1.94-4.10) mg/kg/day for 12 months. The psoriasis area and severity index was reduced by 63-76%. Ambulatory GFR (iothalamate-125I), ERPF (hippuran-131I), RVR and MAP were examined at 3-months intervals. A control renal biopsy was performed shortly before treatment start and a second biopsy was taken after 12 months of therapy. GFR was slightly but significantly reduced after 6 and 9 months; after 12 months the decrease was not significant (121.0 +/- 7.6 versus 115.2 +/- 7.8 ml/min/1.73M2, P > 0.10). After 12 months serum creatinine increased from 82 +/- 4 to 94 +/- 7 mumol/litre (P < 0.05), while an insignificant increase of ERPF was seen and FF decreased from 0.29 +/- 0.01 to 0.26 +/- 0.01 (P < 0.05). MAP remained unchanged. GFR and serum creatinine correlated significantly within each 3-month interval. A slight de novo interstitial fibrosis was seen in the second biopsy in 4 of 10 patients receiving a mean CsA dose of 3.2-4.1 mg/kg/day. In three of these patients a concomitant rise in serum creatinine was seen. In conclusion, low-dose CsA was associated with reversible fall in GFR and potentially progressive structural changes not always accompanied by corresponding functional alterations. One should consider reducing the daily dose of CsA to 3.0 mg/kg bodyweight or less in CsA therapy up to 1 year.
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PMID:Renal effects of maintenance low-dose cyclosporin A treatment in psoriasis. 781 61

Renal effects of FR139317, an endothelin ETA receptor antagonist, were examined using anesthetized normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The intravenous bolus injection of FR139317 (10 mg/kg) produced a slight decrease in mean blood pressure (MAP; -13%) in the control rats and this hypotension was accompanied by a moderate renal vasodilation (renal vascular resistance: RVR; -12%). In the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect (MAP; -26%) accompanied by a potent renal vasodilation (RVR; -33%). FR139317 significantly increased renal blood flow only in the DOCA-salt rats. In contrast, FR139317 produced a significant decrease in urine flow and urinary sodium excretion only in control rats. Northern blot analysis revealed that the renal prepro endothelin-1 (ET-1) mRNA level was significantly increased in DOCA-salt hypertensive rats. Thus, it seems likely that endogenous ET-1 is responsible for the maintenance of DOCA-salt-induced hypertension. We also suggest that at least in part, ET-1 and ETA receptors are involved in renal hemodynamic abnormalities in DOCA-salt-induced hypertension. The augmentation of renal ET-1 production may possibly have a function in the development and maintenance of DOCA-salt-induced hypertension.
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PMID:ETA receptor-mediated role of endothelin in the kidney of DOCA-salt hypertensive rats. 862 4

The effects of amlodipine and perindopril on renal hemodynamics and tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a randomized, double-blind crossover fashion. Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a 2-week placebo washout between treatments. At the end of each period, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as 51Cr-EDTA and 123I-hippuran clearance, respectively, and tubular function evaluated by the lithium clearance technique was determined. Both drugs maintained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) to a similar extent (time x treatment, P = 0.466): amlodipine from 126.9 +/- 2.5 to 115.9 +/- 2.2; perindopril from 126.9 +/- 2.5 to 117.9 +/- 3.9 (time effect of all treatments together, P = 0.003). Accordingly, renal vascular resistance (RVR, mm Hg/mL/min/1.73 m2) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 to 0.30 +/- 0.02; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01 (time effect all treatments together, P = 0.043). Sodium clearance and fractional excretion of sodium were not affected by either drug. Output of fluid from the proximal tubules measured as clearance of lithium (CLi, mL/min) and uric acid (CUr, mL/min) was higher after amlodipine than after perindopril (CLi 19.1 +/- 2.1 v 16.5 +/- 1.7, P =0.036 and CUr 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after amlodipine, distal absolute reabsorption of sodium was higher (DARNa 2.57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid was lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparison with perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent. Overall sodium excretion is not affected by either agent. Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril.
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PMID:Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporine-treated renal allograft recipients. 862 31


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