Abstract:HIROSHI ITOH, KAZUWA NAKAO, TAKAYUKI YAMADA, NARITO MORE, SHOZO SHIONO, AKIRA SUGAWARA,. YOSHMKO SAJTO, MASASHI MUKOYAMA, HIROSHI ARAI, AND HIROO IMURASUMMARY To elucidate the modulatory role of the brain renln-angiotensin system in the regulation of the secretion of atrial natriuretic factor (ANF) from the heart, the effects of intracerebroventricular administration of angiotensin II on the plasma ANF level were examined in conscious unrestrained rats. Administration of angiotensin II in doses of 100 ng and 1… Show more
“…In dogs, Edward et al (23) noted that Ang II infusion increased circulating ANP concentrations. Itoh et al (24) infused Ang II icy into rats and found that under these circumstances the release of ANP in response to saline loads was increased. However, the Ang II-icy was given acutely rather than chronically in their study.…”
Angiotensin (Ang) II and atrial natriuretic peptide (ANP) have opposing effects on blood pressure, sympathetic activity, vasopressin and ACTH secretion, salt appetite, and drinking. We observed their interaction by infusing Ang II (7.2 nmol/h) into the peritoneum (i.p.) or into the lateral ventricle (i.c.v.) of rats with osmotic minipumps for seven days. At sacrifice, rats receiving Ang II-i.c.v. had a systolic blood pressure of 184 +/- 3 (SEM) mmHg, those receiving Ang II-i.p. had 159 +/- 5 mmHg (p < 0.05), while controls had 109 +/- 2 and 110 +/- 2 mmHg, respectively (p < 0.05). Drinking and urine volume increased similarly in rats receiving Ang II by either route, while Uosm decreased. Renin (PRA) values were lower (p < 0.05) in rats receiving Ang II-i.c.v. (0.7 +/- 0.2 ng Ang l/ml/h) or Ang II-i.p. (0.9 +/- 0.2) than in the respective controls (2.3 +/- 0.7 and 2.0 +/- 0.3). Plasma ANP values with Ang II-i.c.v. (18 +/- 1.6 pg/ml) or with Ang II-i.p. (49 +/- 6) were also lower (p < 0.05) than respective controls (89 +/- 12, 76 +/- 4). Vasopressin (AVP) concentrations in the plasma were not influenced by the regimens. In the brain, the ANP contents in areas of the so-called AV3V-region (organum vasculosum laminae terminalis, preoptic periventricular nucleus, medial preoptic nucleus) were similarly and significantly reduced by both Ang II-i.c.v. and Ang II-i.p.. ANP values were also reduced in the median eminence by both types of Ang II-treatment, while ANP concentrations in the supraoptic nucleus were increased. The data show that Ang II infusions producing a chronic rise in blood pressure exert similar effects on drinking behavior, PRA, and ANP concentrations in blood and brain. The AV3V area may be pivotal to both models.
“…In dogs, Edward et al (23) noted that Ang II infusion increased circulating ANP concentrations. Itoh et al (24) infused Ang II icy into rats and found that under these circumstances the release of ANP in response to saline loads was increased. However, the Ang II-icy was given acutely rather than chronically in their study.…”
Angiotensin (Ang) II and atrial natriuretic peptide (ANP) have opposing effects on blood pressure, sympathetic activity, vasopressin and ACTH secretion, salt appetite, and drinking. We observed their interaction by infusing Ang II (7.2 nmol/h) into the peritoneum (i.p.) or into the lateral ventricle (i.c.v.) of rats with osmotic minipumps for seven days. At sacrifice, rats receiving Ang II-i.c.v. had a systolic blood pressure of 184 +/- 3 (SEM) mmHg, those receiving Ang II-i.p. had 159 +/- 5 mmHg (p < 0.05), while controls had 109 +/- 2 and 110 +/- 2 mmHg, respectively (p < 0.05). Drinking and urine volume increased similarly in rats receiving Ang II by either route, while Uosm decreased. Renin (PRA) values were lower (p < 0.05) in rats receiving Ang II-i.c.v. (0.7 +/- 0.2 ng Ang l/ml/h) or Ang II-i.p. (0.9 +/- 0.2) than in the respective controls (2.3 +/- 0.7 and 2.0 +/- 0.3). Plasma ANP values with Ang II-i.c.v. (18 +/- 1.6 pg/ml) or with Ang II-i.p. (49 +/- 6) were also lower (p < 0.05) than respective controls (89 +/- 12, 76 +/- 4). Vasopressin (AVP) concentrations in the plasma were not influenced by the regimens. In the brain, the ANP contents in areas of the so-called AV3V-region (organum vasculosum laminae terminalis, preoptic periventricular nucleus, medial preoptic nucleus) were similarly and significantly reduced by both Ang II-i.c.v. and Ang II-i.p.. ANP values were also reduced in the median eminence by both types of Ang II-treatment, while ANP concentrations in the supraoptic nucleus were increased. The data show that Ang II infusions producing a chronic rise in blood pressure exert similar effects on drinking behavior, PRA, and ANP concentrations in blood and brain. The AV3V area may be pivotal to both models.
“…Additional evidence includes 1) the threshold of the centrally mediated dipsogenic response to Ang II is lower than the pressor response 11 and 2) the brain renin-angiotensin system has been reported to control the release of atrial natriuretic factor, a hormone clearly implicated in volume regulation. 12 Ang II administered centrally, however, releases vasopressin, which has been reported to produce greater pressor effects in male than in female rats. 13 The effects of plasma supernate of dogs on the Na + -K + pump activity of the rat tail artery was independent of gender.…”
This study was designed to investigate the relation between gender, an endogenous inhibitor of the Na + -K + pump, and volume-dependent hypertension induced by stimulation of the brain renin-angiotensin system and increased salt intake. Angiotensin II (20 ng/min i.cv.) was infused for 4 weeks in five dogs of each sex with saline as the drinking fluid. In male dogs, angiotensin II induced parallel pressor (30%) and dipsogenic responses (70%), whereas no hypertension and no increase in fluid intake were observed in females. In contrast, the activity of the Na + -K + pump as assessed by **Rb uptake was independent of gender. Our data provide novel evidence that gender plays a determining role in the physiological properties of centrally administered angiotensin n . Presently, the role of gender in the hypertension induced by long-term stimulation of the brain reninangiotensin system remains unknown. We 6 and Balda et al 7 have presented evidence that an endogenous inhibitor of the Na + -K + pump might be implicated in the development of hypertension due to long-term stimulation of the brain renin-angiotensin system and an increase in salt intake. This study investigated the role of gender in the development of hypertension resulting from longterm intracerebroventricular administration of Ang II to awake instrumented dogs receiving 0.9% sodium chloride solution as the drinking fluid. The relation between hypertension and the presence of an endogenous inhibitor of the Na + -K + pump was also determined.
MethodsTen dogs, five of each sex (seven mongrels and three beagles; males 12.8-20.2 kg, mean 14.85 kg; females 16.4-21.5 kg, mean 18.8 kg), were anesthetized with thiopental (30 mg/kg i.v.), intubated, and prepared for sterile surgery. Under aseptic conditions, a heparin-filled Tygon catheter (0.125 in. o.d., 0.0625 in. i.d.) was implanted into the abdominal aorta via the iliac artery. A left thoracotomy was performed through the fourth intercostal space and an electromagnetic flow probe (14-16 mm, Micron Inc., Los Angeles, California) was placed around the pulmonary artery. The catheter and transducer leads were tunneled subcutaneousry to the dorsum of the neck and secured in place after closure of the thoracotomy. The dogs received ampicillin (20 mg/ kg) and streptomycin (1 g) intramuscularly for 4-5 days after surgery. The aortic catheter was flushed daily with heparin solution (1,000 units/ml). None of the females were in estrus during the study.
Experimental ProtocolAnimals were permitted to recover from surgery for approximately 10 days. After the recovery period, each dog received tap water as the drinking fluid for 5 days (control tap water), followed by by guest on May 9, 2018 http://hyper.ahajournals.org/ Downloaded from
“…11B). 8,9,59–65) Furthermore, the natriuretic peptide system has therapeutic implications for vascular regeneration in patients with arteriosclerosis obliterans. 48)…”
Section: Translational Research On Endocrinology and Metabolismmentioning
Translation is the process of turning observations in the laboratory, clinic, and community into interventions that improve the health of individuals and the public, ranging from diagnostics and therapeutics to medical procedures and behavioral changes. Translational research is defined as the effort to traverse a particular step of the translation process for a particular target or disease. Translational science is a newly emerging science, distinct from basic and clinical sciences in biology and medicine, and is a field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. Advances in translational science will increase the efficacy and safety of translational research in all diagnostic and therapeutic areas. This report examines translational research on novel hormones, the natriuretic peptide family and leptin, which have achieved clinical applications or for which studies are still ongoing, and also emphasizes the lessons that translational science has learned from more than 30 years' experience in translational research.
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