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)

Evidence that the renal sympathetic nerves have direct effects on renal tubular function suggests that neurogenic mechanisms may play an important role in the daily regulation of sodium balance. We evaluated the influence of the renal nerves on the rate of elevating urinary sodium excretion (UNaV) after a step increase in fixed sodium intake. Conscious rats with innervated (INN) or denervated (DNX) kidneys were placed on low-sodium intake (LNa = 0.3 meq/day) or a normal sodium intake (NNa = 1.0 meq/day) by intravenous infusion. Hourly changes in UNaV were determined 24 h before and 72 h after increasing sodium intake to either NNa or high-sodium intake (HNa = 5.0 meq/day). Switching from LNa to NNa, INN rats increased UNaV within 24 h; however, DNX rats did not begin to increase UNaV until hour 60. Cumulative sodium balance over 72 h was more positive in DNX rats (INN = 1.29 +/- 0.29 meq; DNX = 2.06 +/- 0.21 meq, P less than 0.05). During the LNa-to-HNa switch, both INN and DNX rats increased UNaV equally for 12 h; however, at this time INN rats continued to increase UNaV, whereas DNX rats did not. DNX rats had a net accumulation of 2.54 meq more sodium than INN rats over 72 h. Significant inhibition of plasma renin activity within the first 24 h occurred only in rats receiving the LNa-to-HNa switch in sodium intake, and this response was not different between rats with innervated and denervated kidneys. These data suggest that the renal nerves provide a rapid sodium excretory response to step increases in sodium intake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neurogenic regulation of rate of achieving sodium balance after increasing sodium intake. 187 52

We have reported that the angiotensin II (Ang II) AT1 receptor antagonist losartan markedly lowers arterial pressure in sodium-replete, normotensive rats. We hypothesized that this action of losartan was mediated by its blocking the effects of endogenous Ang II. To test this hypothesis, rats were instrumented with arterial and venous catheters for measurement of arterial pressure and infusion of losartan, respectively. After 3 days of control measurements, losartan was infused for 10 days (10 mg/kg/d) in rats on a normal daily sodium intake (NNa; approximately 2 mmol/d, n=6) and rats on a high daily sodium intake (HNa; approximately 15 mmol/d, n=7) to suppress endogenous Ang II. Although basal plasma renin activity was markedly suppressed in HNa rats (0.9 +/- 0.4 ng Ang I/ mL/h) compared with NNa rats (4.0 +/- 0.3 ng Ang I/mL/h), control arterial pressure was not different between NNa (113 +/- 4 mm Hg) and HNa (113 +/- 2 mm Hg) rats. Losartan decreased arterial pressure from control levels in NNa rats on the first day of infusion (-12 +/- 2 mm Hg) but had no effect on arterial pressure in HNa rats (+4 +/- 4 mm Hg). Furthermore, by day 10 of losartan infusion, arterial pressure had decreased further from control levels in NNa rats (-32 +/- 2 mm Hg) but remained unchanged compared with control in HNa rats (+5 +/- 6 mm Hg). A second study was conducted to test the hypothesis that the area postrema, a circumventricular organ proposed to mediate the long-term neurogenic pressor activity of Ang II is a site of action for losartan. After 3 control days, losartan was administered for 10 days to area postrema-lesioned rats (APx; n=11) or sham-lesioned rats (n=10) consuming an NNa diet. Control arterial pressure was similar in sham (95 +/- 3 mm Hg) and APx (96 +/- 2 mm Hg) rats. Basal plasma renin activity was not different between groups (sham, 4.1 +/- 1.5 versus APx, 5.3 +/- 1.6 mm Hg Ang I/mL/h). On day 1 of losartan treatment, arterial pressure decreased to a significantly lower level in sham (80 +/- 2 mm Hg) compared with APx (90 +/- 3 mm Hg) rats. This trend continued through day 4 of losartan infusion, in which arterial pressure in sham rats (72.2 +/- 2 mm Hg) was significantly lower than in APx rats (83 +/- 4 mm Hg). However, during the remainder of the losartan infusion, there were no significant differences between groups with the exception of day 8 (sham, 72 +/- 2 mm Hg; APx, 84 +/- 2 mm Hg). Taken together, these results support the hypothesis that the hypotensive actions of losartan in sodium-replete, normotensive rats are due to blockade of the physiological effects of endogenous Ang II. Furthermore, an intact area postrema is essential for full expression of the hypotensive actions of losartan in normal rats.
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PMID:Hypotensive response to losartan in normal rats. Role of Ang II and the area postrema. 861 10

The regulation of blood pressure and sympathetic outflow by the brain renin-angiotensin system in animals subjected to raised or lowered dietary Na(+) intake is unclear. This study compared the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to intracerebroventricular (i.c.v.) infusion of angiotensin II (AngII) and III (AngIII) before and after peripheral V(1) receptor blockade (V(1)B) in alpha-chloralose-urethane-anaesthetized rats fed a low (0.03%, LNa(+)), normal (0.3%, NNa(+)) or high Na(+) diet (3.0%, HNa(+)) from 4 to 11 weeks of age. The rise in MAP 2 min post AngII i.c.v. was greater in HNa(+) (14 +/- 3 mmHg) versus LNa(+) (8 +/- 1 mmHg, P < 0.05) and after AngIII i.c.v. in HNa(+) (14 +/- 3 mmHg) versus NNa(+) (6 +/- 1 mmHg, P < 0.05) and LNa(+) (7 +/- 1 mmHg, P < 0.05). The MAP responses to AngII and AngIII i.c.v. were abolished after V(1)B in LNa(+), but were only attenuated in HNa(+). In NNa(+), V(1)B blunted the MAP responses to AngII and abolished those to AngIII. The MAP remained elevated 30 min after AngII in all groups, but returned to baseline levels 15 min after AngIII in NNa(+) and HNa(+) (P < 0.01). Twenty minutes after i.c.v. AngII, RSNA rose above baseline in HNa(+) (112 +/- 1%), a response not observed in the LNa(+) and NNa(+) groups. Twenty minutes post AngIII i.c.v., RSNA was elevated in both HNa (109 +/- 2%) and NNa(+) (109 +/- 2%). After V(1)B, RSNA rose only in the HNa(+) group 15 min post AngIII infusion (109 +/- 1%). Together, these findings: (1) suggest that HNa(+) intake augments the MAP and RSNA responses to i.c.v. AngII and AngIII; (2) highlight an important role for peripheral V(1) receptors during these responses; and (3) differentiate the effects of AngII and AngIII on blood pressure and RSNA.
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PMID:Influence of dietary sodium on the blood pressure and renal sympathetic nerve activity responses to intracerebroventricular angiotensin II and angiotensin III in anaesthetized rats. 1988 May 39