Angiotensin-converting enzyme inhibition by lisinopril enhances liver regeneration in rats

Bradykinin has been reported to act as a growth factor for fibroblasts, mesangial cells and keratinocytes. Recently, we reported that bradykinin augments liver regeneration after partial hepatectomy in rats. Angiotensin-converting enzyme (ACE) is also a powerful bradykinin-degrading enzyme. We have investigated the effect of ACE inhibition by lisinopril on liver regeneration after partial hepatectomy. Adult male Wistar rats underwent 70 percent partial hepatectomy (PH). The animals received lisinopril at a dose of 1 mg kg body weight-1 day-1, or saline solution, intraperitoneally, for 5 days before hepatectomy, and daily after surgery. Four to six animals from the lisinopril and saline groups were sacrificed at 12, 24, 36, 48, 72, and 120 h after PH. Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen using the PC-10 monoclonal antibody. The value for the lisinopril-treated group was three-fold above the corresponding control at 12 h after PH (P<0.001), remaining elevated at approximately two-fold above control values at 24, 36, 48 (P<0.001), and at 72 h (P<0.01) after PH, but values did not reach statistical difference at 120 h after PH. Plasma ACE activity measured by radioenzymatic assay was significantly higher in the saline group than in the lisinopril-treated group (P<0.001), with 81 percent ACE inhibition. The present study shows that plasma ACE inhibition enhances liver regeneration after PH in rats. Since it was reported that bradykinin also augments liver regeneration after PH, this may explain the liver growth stimulating effect of ACE inhibitors

Induction of the c-fos proto-oncogene in the rat pineal gland during stress

To investigate the effects of stressful stimuli on pineal gland activity, male Wistar albino rats (200-250 g, 2-4 per group) were submitted to 30 min of forced immobilization or to unilateral vibrissotomy 30 min before sacrifice. In situ hybridization was performed with a 35S-labelled 50-base oligonucleotide probe complementary to nucleotides 270-319 of rat c-fos on sections containing the pineal gland. Autoradiograms were quantified using a JAVA microdensitometer. Stressful stimuli induced a significant increase in the expression of c-fos mRNA in the pineal gland (restraint = 144.3 +/- 14.4 cpm/mm2; hemivibrissotomy = 206.7 +/- 29.5 cpm/mm2) as compared to no restraint animals (30.6 +/- 5.1 cpm/mm2), animals displaying tonic-clonic seizures after an ip (64 mg/kg) injection of pentylenetetrazole (34.0 +/- 4.7 cpm/mm2), or competition (70.6 +/- 11.4 cpm/mm2) and RNAase-treated (52.7 +/- 9.1 cpm/mm2) controls. These results raise the possibility that stressful stimuli may interfere with pineal gland function

Pressor effects of acetylcholine microinjected into forebrain nuclei of unanesthetized rats

The injection of 13.5-54 nmol/500 nl of acetylcholine (ACH) into different brain areas of unanesthetized freely-moving 200-250 g male Wistar rats caused only pressor responses. In the prosencephalon, the lateral septal area was the site at which ACH was more effective, whereas injections into surrounding areas, such as the accubens/bed nucleus striae terminalis, the medial septal area or the lateral ventricle were less effective. No effective. No blood pressure effects were observed after injection into the anterior amygdala. In the diencephalon, the ventromedial hypothalamic nucleus was the most sensitive site, whereas injection of ACH into surrounding areas, such as the posterior and lateral hypothalamic or the dorsal and ventral prtemammillary nuclei was less effective. At all sites tested, the local pretreatment with 138-276 nmol atropine abolished the pressor response to ACH, suggesting a mediation through muscarinic receptors. The sites of injection were confirmed histologically. The present data indicate the existence of a cholinergic-sensitive site involved in the control of blood pressure at the level of the lateral septal area

Chemical lesion of the circumventricular organs with monosodium glutamate reduces the blood pressure of spontaneously hypertensive but not of one kidney-one clip hypertensive rats

Subcutaneous injection of monosodium glutamate (MSG) on days 1, 5 and 9 of the experiment (5g/kg per day) significantly reduced the blood pressure of a group of 10 spontaneously hypertensive rats (SHR) measured 7 and 14 days after treatment (200 ñ 7 mmHg vs 172 ñ 8 mmHg or 185 ñ 3 mmHg, respectively) without affecting that of 11 age-matched Wistar Kyoto (WKY) rats (127 ñ 7 mmHg and 119 ñ 5 mmHg, respectively). Using autoradiographic methods and 125 I-Sar 1-angiotensin II, receptor binding was shown to be higher in the subfornical organ (SFO) of SHR (332 ñ 31 fmol/mg protein) when compared to WKY rats (240 ñ 30 fmol/mg protein) and similar (222 ñ 21 vs 170 ñ 14 fmol/mg protein) in the paraventricular (PVN). Binding to angiotensin-converting enzyme (ACE) was evaluated using the ACE inhibitor 125 I-35 A as ligand. Binding to ACE was lower in SHR in the PVN and the globus pallidus (GP) of SHR when compared to WKY rats (PVN: 111 ñ 9 vs 172 ñ 13 and GP: 163 ñ 2 vs 213 ñ 7 fmol/mg protein) and similar in the SFO, choroid plexus (ChP) and caudate nucleus (CD) of both strains (SFO: 779 ñ 107 vs 805 ñ 169; ChP: 2, 780 ñ 210 vs 3, 140 ñ 360 and CD: 461 ñ 42 vs 424 ñ 18 fmol/mg protein). No changes in angiotensin II (Ang II) receptor number or binding to ACE were detected in thesebrain areas after MSG treatment of SHR or WKY rats. Similar MSG treatment did not affect the development of one kidney-one clip (1K-1C) experimental hypertension in a group of 10 Wistar rats when compared a group of 8 saline-treated animals. 1K-1C surgery was performed 7 days after MSG treatment and blood pressure measured before (saline 123 ñ 1 mmHg vs MSG 126 ñ 1 mmHg) and both 7 (151 ñ 4 mmHg vs 158 ñ 3 mmHg) and 15 days (163 ñ 4 mmHg vs 172 ñ 6 mmHg) after surgery. The results support the hypothesis of a differential role of central MSG-sensitive mechanisms in genetic and experimental renal forms of hypertension