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Biomedical subjects

K Kohara

Publications and source records attributed to K Kohara.

At least 109 records · Page 6Linked to original sources
PubMed1989

Increase in the blood pressure and decrease in the norepinephrine release in the ventrolateral medulla during intraventricular administration of hypertonic NaCl.

Norepinephrine (NE) release in the ventrolateral medulla (VLM) was serially measured in anesthetized male Wistar rats during the rise in the blood pressure (BP) produced by acute intraventricular (ICV) administration of hypertonic (1.5 M) NaCl. Catecholamine release was determined by a brain microdialysis method using high performance liquid chromatography and electrochemical detector. The release of NE in the VLM was significantly decreased after ICV 1.5 M NaCl. In another set of rats, the pressor response to acute ICV 1.5 M NaCl was attenuated by selective administration of NE to the VLM using the microdialysis method. Chronic and continuous ICV infusion of 1.5 M NaCl to conscious rats caused an increase in BP on day 10 which was associated with a decrease in NE release in the VLM; concomitant ICV infusion of NE or of a synthetic NE precursor, L-threo-3,4-dihydroxyphenylserine (L-DOPS) prevented the rise in BP as well as the reduction in NE release. These results suggest that a decrease in the NE release of the VLM may contribute to the change in BP induced by ICV infusion of hypertonic saline.

Animals↗
PubMed1989

Effect of volume expansion on hemodynamic variables in nephrectomized dogs.

We have previously demonstrated that blood pressure elevation by acute blood volume expansion is volume-dependent during the infusion period and resistance-dependent in the post-infusion period in normal anesthetized dogs, and that such an increase in blood pressure is associated with a potentiation of the pressor response to norepinephrine. To evaluate the possible renal contribution to these hemodynamic changes, blood volume expansion was performed for 1 h with dextran dissolved in lactated Ringer's solution (20 ml/kg) in 15 nephrectomized dogs. The mean blood pressure, cardiac output and total peripheral resistance at the end of infusion were 126%, 225% and 60%, respectively; 3 h after volume expansion they were 126%, 151%, and 92% respectively. However, in 4 dogs, there was an increase in mean blood pressure (138%) 3 h after volume expansion. This was thought to result from an increase in the total peripheral resistance (133%) associated with the recovery of cardiac output (106%). The pressor response to norepinephrine (0.5 microgram/kg) was potentiated after volume expansion. These results indicate that the handling of volume by the kidney contributed to the maintenance of an elevated level of cardiac output. However, nephrectomy did not seem to interfere with the hemodynamic switching of the causative factor for blood pressure elevation from increased cardiac output to increased total peripheral resistance. Neither was the potentiation of pressor response to norepinephrine affected.

Animals↗
PubMed1989

Effects of the baroreceptor reflex system on atrial natriuretic factor secretion during volume expansion in dogs.

1. The purpose of this study was to determine whether the baroreceptor reflex system affects the secretion of atrial natriuretic factor directly or indirectly during acute volume expansion. 2. Lactated Ringer's solution containing low mol. wt. dextran was infused at 20 ml/kg for 1 h into dogs in which baroreceptors had been denervated surgically (Vx), dogs in which the autonomic system had been blocked with hexamethonium (Hx) and control dogs. 3. The plasma noradrenaline level was significantly higher in the Vx group and lower in the Hx group than in the control group throughout the experiment. The plasma levels of arginine vasopressin in the Vx and Hx groups were significantly higher than in the control group. 4. The plasma atrial natriuretic factor levels in the three groups showed similar increases during and after volume expansion. 5. The plasma atrial natriuretic factor level was significantly correlated with the right atrial pressure during volume expansion. 6. From these results, it seems unlikely that changes in the plasma level of atrial natriuretic factor during volume expansion are regulated by the baroreceptor reflex directly or indirectly by systemic changes in the sympathetic nervous system or arginine vasopressin secretion.

Animals↗
PubMed1989

Synergism of intraventricular NaCl infusion and subpressor angiotensins in rats.

The effect of selective salt infusion to the central nervous system on the blood pressure (BP) regulation was examined in male Wistar rats. Hypertonic NaCl (0.8 M, 1 microliter/h) was infused into the lateral ventricle concomitantly with intravenous infusion of a subpressor dose (5.4 pmol.kg-1.min-1) of angiotensin II (ANG II) or its analogues for 7 days using osmotic minipumps. The BP was not increased by intracerebroventricular infusion of NaCl alone at this dose but was significantly and consistently increased by concomitant intravenous infusion of ANG II or its analogues. The increases in the BP over the base-line values on day 7 in groups on infusions of ANG II, ANG III, and pentasarcosyl-ANG II [(Sar)5ANG II] were 29 +/- 5 mmHg (n = 9, P less than 0.05), 8 +/- 2 mmHg (n = 8, P less than 0.05), and 19 +/- 3 mmHg (n = 6, P less than 0.05), respectively. The responses to hexamethonium, prazosin, and antagonists of arginine vasopressin and ANG II were examined in separate sets of conscious and unrestrained animals that had received intracerebroventricular infusion of NaCl and intravenous infusion of ANG II for the preceding 6 days. These animals showed significantly greater depressor responses only to hexamethonium and prazosin than control. These results indicate that the pressor effect of continuous and concomitant administration of intracerebroventricular NaCl and intravenous ANG II is mainly due to activation of the sympathetic nerve function. Synergism of the effects of selective central sodium administration and a subpressor dose of ANG II in the central nervous system is suggested.

Angiotensins↗
PubMed1989

Contribution of the baroreflex afferent nerves to the production of vasoconstricted hypertension in volume-expanded dogs.

Dextran in lactated Ringer's solution (20 ml/kg) was infused for 1 hour into anesthetized dogs with sinoaortic denervation and vagotomy (deafferentation; n = 10) and dogs treated with hexamethonium (de-efferentation; n = 13) to compare with our previous observation in dogs with an intact autonomic nervous system (control, n = 34). During the infusion, increase in blood pressure associated with increase in cardiac output was observed in all three groups. The increases in blood pressure were larger in the two groups with an impaired autonomic nervous system. In the recovery period, the control dogs and the hexamethonium-treated dogs showed gradual increases in total peripheral resistance and in vasoconstricted hypertension 3 hours after stopping the infusion. In contrast, the dogs with sinoaortic denervation and vagotomy did not show any increase in total peripheral resistance. The vasoconstricted groups showed peaks of natriuresis soon after the infusion, not 3 hours after the infusion when vasoconstriction was observed, although the dogs with deafferentation did not show a significant increase in natriuresis. Norepinephrine (0.5 micrograms/kg) was administered intravenously before and after volume expansion, and the pressor responses in the three groups after volume expansion were enhanced similarly (143%, 128%, and 136%, respectively). These results indicate that the afferent signals from peripheral vessels to the brain contribute to the production of vasoconstricted hypertension after acute volume expansion and that the vasoconstriction is independent of pressor hypersensitivity and is dissociated in time from the natriuresis.

Afferent Pathways↗
PubMed1989

Direct vascular effects of 19-hydroxyandrostenedione.

A C19 steroid, 19-hydroxyandrostenedione (19-OHAD), an amplifier of the mineralocorticoid effects of aldosterone, is known to cause hypertension in rats during chronic administration. In the present study we examined the direct vasoconstrictive effects of 19-OHAD and aldosterone in vitro as a possible mechanism of their hypertensinogenic effects. Contractile responses of central ear arteries from normal male rabbits to either 19-OHAD or aldosterone were examined in Krebs' bicarbonate buffer. When given alone, neither 19-OHAD nor aldosterone consistently caused contraction of the arteries, nor did 19-OHAD amplify the contractile action of aldosterone to a detectable range. Pretreatment of the ear arteries with desipramine, an inhibitor of neuronal uptake (uptake 1) of norepinephrine (NE), resulted in significant concentration-dependent contraction by each steroid. This contraction was markedly attenuated by prazosin but not by yohimbine. Both steroids significantly potentiated the contractile reaction of the ear arteries to exogenous NE in a dose-related manner without pretreatment with desipramine, suggesting that 19-OHAD may increase vascular resistance through the inhibition of extraneuronal NE uptake (uptake 2). These results suggest that 19-OHAD is not an amplifier of aldosterone at the vascular site.

Aldosterone↗
PubMed1988

Potentiation of the pressor effect of angiotensin II by intraventricular infusion of hypertonic saline.

The effect of selective NaCl loading to the brain on the blood pressure regulation was examined in male Wistar rats. Hypertonic NaCl (0.8M, 1 microL/h) was infused for 7 days into the lateral ventricle (ICV) along with intravenous (IV) infusion of angiotensin II (AII) at a dose of 5.4 pmol/kg per minute. Although neither ICV hypertonic NaCl or IV AII infusion alone had any substantial pressor effect, concomitant administration of these resulted in a consistent and significant increase in the blood pressure on day 7 over the baseline value, amounting to 29 +/- 5 mm Hg (n = 9; P less than 0.001). Inasmuch as the increase in the BP was totally prevented by intraperitoneal injection of guanethidine (40 mg/day), hyperactivity of the sympathetic nervous system appears, at least in part, responsible for the BP elevation caused by the combination of ICV hypertonic NaCl and IV subpressor AII infusion.

Angiotensin II↗
PubMed1988

Vasoconstriction and hypersensitivity to vasoactive substances after acute volume expansion in dogs.

In a search for factors contributing to the sustained blood pressure (BP) elevation in acutely volume-loaded animals, dextran dissolved in lactated Ringer's solution (20 ml/kg) was infused into 34 mongrel dogs over a period of 1 hour under pentobarbital anesthesia and changes in hemodynamic and humoral variables were monitored during its infusion and for 3 hours after its infusion. BP elevation during volume loading (from 114 +/- 3 to 128 +/- 3 [SEM] mm Hg) was attributed to an increase in cardiac output. After volume loading, some dogs maintained BP elevation whereas others did not. The former group showed an increase in total peripheral resistance, demonstrating a transformation of cardiac output to total peripheral resistance as a responsible factor in maintenance of the elevated BP. The plasma levels of norepinephrine, vasopressin, and plasma renin activity were not elevated, indicating that these vasoactive factors were not responsible for elevation of the BP or total peripheral resistance. The changes in the hematocrit, atrial natriuretic factor, urine volume, and urinary sodium excretion were identical in the two groups, and natriuresis was not prominent when total peripheral resistance was high. Pressor responses to norepinephrine and angiotensin II were potentiated 3 hours after stopping infusion in both groups, but this potentiation was not correlated with the increase in total peripheral resistance or mean BP. Thus, acute volume expansion produced resistance-dependent hypertension following the initial volume-dependent hypertension. It is unlikely that a vascular sensitizing natriuretic factor plays a role in the resistance-dependent BP elevation. The mechanism and physiological importance of hypersensitivity to vasoactive substances remain to be elucidated.

Aldosterone↗
PubMed1988

Central sodium loading modifies norepinephrine content in the ventrolateral medulla and blood pressure in rats.

We evaluated the effects of intracerebroventricular (ICV) infusion of hypertonic NaCl on blood pressure (BP) control as well as on NE content in the ventrolateral medulla (VLM). Nine groups of Wistar rats received 10 day's ICV infusion of NaCl solutions containing either norepinephrine (NE, 1.3 micrograms/min) or a synthetic NE precursor, 1-threo-3,4-dihydroxyphenylserine (1-DOPS, 17 micrograms/min) for 3 concentrations (0.15M, 0.8M or 1.5M) of NaCl. On day 9, only the group on ICV infusion of 1.5M NaCl alone had a significant rise in BP (133 +/- 3 mmHg, P less than 0.05 vs control) while other groups remained normotensive. The ICV infusion of 1.5M NaCl reduced NE content, determined by a microdialysis method, in the VLM while the concomitant ICV infusion of NE or 1-DOPS restored it suggesting that the decrease in NE content in the VLM may be a contributing factor in the BP elevation by the central salt loading.

Animals↗
PubMed1987

Contribution of elevated peripheral resistance to acute volume loaded hypertension in dogs.

The role of peripheral resistance in volume loaded hypertension was examined by measuring changes in hemodynamic and humoral factors during dextran infusion for one hour, and for three hours after stopping the infusion in 30 anesthetized dogs. The mean blood pressure was elevated significantly (118%, p less than 0.01), accompanied by increased cardiac output (170%, p less than 0.01) during volume loading. In the recovery period, cardiac output returned to the basal level while the total peripheral resistance gradually increased (118%, p less than 0.01) contributing to the maintenance of high blood pressure (108%, p less than 0.01). There was no significant correlation between the hematocrit change and the increase in peripheral resistance in the recovery period. The levels of plasma norepinephrine, epinephrine, renin activity and vasopressin were suppressed by volume loading. These results demonstrated the importance of increase in peripheral resistance for maintaining high blood pressure in this acute volume excess model. The participation of the renin-angiotensin system, the sympathetic nervous system and vasopressin were all excluded and vascular structural changes were most unlikely to be involved in this acute experiment. It remains unknown whether this conversion is attributable to the summation of local autoregulation or to some other factors.

Animals↗
PubMed1987

Extra-adrenal pheochromocytoma manifesting renovascular hypertension.

A case with extra-adrenal pheochromocytoma, which was found by chance in the course of renovascular hypertension, is reported. The tumor was on the stenotic portion of the right renal artery. The results of examinations for pheochromocytoma were not conclusive, that is, inconsistent elevation of plasma catecholamines and urinary catecholamine excretion, equivocal results of pharmacological tests for pheochromocytoma, and negative results in [131I]metaiodobenzylguanidine scintigraphy. The stenosis of the right renal artery disappeared, the blood pressure was normalized by surgical resection of the tumor, and the extra-adrenal pheochromocytoma was finally diagnosed by pathohistological findings. Renovascular hypertension appeared to be the primary cause of this hypertension, judging from the significant decrease in blood pressure induced by an angiotensin II analog and a renal vein renin ratio of 7.3. Even in the case of obvious renovascular hypertension, the possibility of this unusual coexistence with pheochromocytoma should be considered.

Adult↗
PubMedDate not supplied

Effect of ouabain on hemodynamics in acute volume expanded hypertensive dogs.

To evaluate possible roles of endogenous Na+-K+-ATPase inhibitors in vasoconstricted blood pressure elevation produced by acute volume expansion, we administered ouabain (Na+-K+-ATPase inhibitor) intravenously (30 micrograms/kg) for 10 min to dogs, 3 h after volume expansion with dextran in lactated Ringer's solution (20 ml/kg, for 1 h). Acute volume expansion resulted in the elevation of blood pressure associated with an increase in cardiac output. In some dogs the blood pressure remained elevated with gradual increase in total peripheral resistance (Group I) or with sustained high cardiac output (Group II), and in other dogs (Group III) it returned to the control level. Ouabain administration elevated the blood pressure and total peripheral resistance in these groups and sham dogs which did not have volume expansion. And these effects of ouabain were not correlated with the degree of blood pressure or vasoconstriction produced by volume expansion. Thus, it is not likely that endogenous Na+-K+-ATPase inhibitors increased to produce vasoconstricted hypertension after acute volume expansion.

Animals↗
PubMedDate not supplied

Reassessment of plasma angiotensins measurement: effects of protease inhibitors and sample handling procedures.

Characterization of C- and N-terminal forms of angiotensin (Ang) peptides mandated assessment of methods to determine plasma levels. 125I-Ang I, 125I-Ang II, and 125I-Ang(1-7) were added to blood samples in the presence of protease inhibitors. Ethylenediaminetetraacetic acid (EDTA) inhibited the conversion of 125I-Ang I to 125I-Ang II. o-Phenanthroline and EDTA (EDTA + o-Ph) did not eliminate [des-Asp1] fragments or 125I-Ang(1-7). The combination of EDTA + o-Ph and pepstatin A or 4-(chloromercuri) benzoic acid (PCMB) significantly reduced 125I-Ang(1-7) generation. Only PCMB plus EDTA + o-Ph eliminated [des-Asp1] fragments. Authentic plasma values of Ang peptides require the correct choice of protease inhibitors.

Angiotensin I↗
PubMedDate not supplied

Angiotensin(1-7) in the spontaneously hypertensive rat.

We profiled the concentrations of angiotensin I (Ang I), angiotensin II (Ang II), and angiotensin(1-7) [Ang(1-7)] by the combination of radioimmunoassay and high performance liquid chromatography in the blood of 14-week-old male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) drinking either tap water or a solution containing ceranapril (30 mg/kg) or lisinopril (20 mg/kg) for 14 days. Differences in the chemical and pharmacokinetic properties of the two converting enzyme inhibitors ruled out class-related effects. Plasma renin activity, angiotensin converting enzyme (ACE) activity, and plasma levels of Ang I and Ang II were the same in vehicle-treated WKY and SHR. In contrast, plasma levels of both Ang(1-7) and vasopressin in SHR were 3.7-fold and 2.6-fold higher, respectively (p < 0.05). Angiotensin converting enzyme inhibition reduced the blood pressure of WKY and SHR, and augmented their intake of water and output of urine. These changes were associated with increases in renin activity and plasma levels of Ang I and Ang(1-7). In both WKY and SHR, lisinopril had a greater effect in inhibiting plasma and cerebrospinal fluid ACE, reducing levels of plasma angiotensinogen, and increasing the concentrations of authentic Ang II. The principal finding of this study is that plasma Ang(1-7) is the sole component of the circulating angiotensin system that is elevated in the established phase of genetic hypertension. The finding that chronic inhibition of ACE augments circulating levels of Ang(1-7) evidenced the existence of functional pathways for the alternate processing of Ang I.

Angiotensin I↗