Search PubMed⌕ Search

Biomedical subjects

K Kohara

Publications and source records attributed to K Kohara.

At least 91 records · Page 5Linked to original sources
PubMed1994

Glucose intolerance exaggerates left ventricular hypertrophy and dysfunction in essential hypertension.

The influence of glucose intolerance, the preclinical stage of diabetes mellitus, on the progression of left ventricular hypertrophy and left ventricular dysfunction in essential hypertension, was assessed with two-dimensional M-mode echocardiography in age- and sex-matched essential hypertensive patients with (n = 28) or without (n = 44) glucose intolerance, and normotensive control subjects (n = 29). Left ventricular mass index in hypertensive patients with glucose intolerance was significantly higher than that in hypertensive patients without glucose intolerance (mean +/- SD, 115.6 +/- 28.2 v 102.1 +/- 22.1 g/m2; P < .05). Left ventricular diastolic function as reflected by peak lengthening rate was reduced in glucose-intolerant hypertensive patients than in hypertensive patients without glucose intolerance (2.68 +/- 0.71 v 3.16 +/- 0.82/sec; P < .05). End-systolic wall stress/left ventricular end-systolic volume index, an index of left ventricular contractility, was reduced more in glucose-intolerant hypertensive patients than in hypertensive patients without glucose intolerance (2.75 +/- 0.55 v 3.13 +/- 0.55 10(3) dyn.m2/cm2.mL-1; P < .01). These findings suggest that glucose intolerance accelerates progression of left ventricular hypertrophy and deteriorates left ventricular diastolic function and contractility in essential hypertension.

Blood Glucose↗
PubMed1994

A case of central diabetes insipidus with spontaneous remission after 8 years of the disease.

A 55-year-old male smoker developed polyuria and polydipsia in November 1983. A water deprivation study revealed a defect in the urine concentrating function, which was corrected by vasopressin. Plasma antidiuretic hormone (ADH) was not increased by smoking. His condition was well controlled by deamino-D-arginine vasopressin. However, since February 1992 he has become completely free from the need for medication to control his urine volume. Re-evaluation studies with water deprivation and smoking revealed dramatic improvements in the urine concentrating function and ADH response. A patient with idiopathic diabetes insipidus with spontaneous remission after 8 years is reported.

Diabetes Insipidus↗
PubMed1994

The effects of central administration of angiotensin II type-1 receptor antagonist, CV-11974, in nephrectomized spontaneously hypertensive rats.

1. The role of the brain renin-angiotensin system in the pathogenesis of genetic hypertension was evaluated using a specific non-peptide angiotensin II type-1 receptor antagonist, TCV-116. 2. CV-11974 (active metabolite of TCV-116) was acutely injected either intravenously (i.v.) or intracerebroventricularly (i.c.v) in male spontaneously hypertensive rats (SHR; 12 week old). In separate groups of nephrectomized and sham-operated SHR, graded doses of CV-11974 were administered either i.v. or i.c.v. for 2 days using an osmotic minipump. In another group, the effects of nephrectomy on the depressor effect of chronic treatment with CV-11974 were investigated. Haemodynamics at three points: before infusion, before nephrectomy and 48 h after nephrectomy, were monitored. 3. Acute i.c.v. injection of CV-11974 decreased blood pressure in the presence of the kidney. Prolonged i.c.v. administration of the drug for 2 days decreased blood pressure even at the lowest dosage, which had no hypotensive effects when given i.v. The hypotensive effect of centrally administered CV-11974 was noted even 48 h after bilateral nephrectomy. 4. These results suggest that the brain renin-angiotensin system has a primary role in the maintenance of hypertension after eliminating the circulating renin-angiotensin system in SHR.

Angiotensin Receptor Antagonists↗
PubMed1994

Differential control of vascular tone and heart rate by different amino acid neurotransmitters in the rostral ventrolateral medulla of the rat.

1. To test the hypothesis that a central mechanism may play a role in the minimal reflex tachycardia noted in response to peripheral converting enzyme inhibition, we compared the effects of intravenous (i.v.) ceronapril (CER) with nitroglycerin (NTG) on neurotransmitter release in the rostral ventrolateral medulla (RVLM), using an in vivo microdialysis method in pentobarbital anaesthetized rats. 2. CER (0.1 mg/kg, i.v.) caused a progressive decrease in glutamate (GLU) release (CER 65 +/- 7% vs NTG 83 +/- 3% of each baseline at 140 min, P < 0.05) and attenuated the increase in glycine (GLY) release (CER 100 +/- 8% vs NTG 122 +/- 9%, P < 0.05). 3. Prevention of blood pressure reduction due to i.v. CER by concomitant infusion of a subpressor dose of angiotensin II (AII) attenuated the progressive reduction of GLU release (87 +/- 4%, P < 0.05 compared with NTG group), whereas GLY release was not affected (106 +/- 5%, NS compared with NTG group). 4. Perfusion of GLU into this area at approximately physiological concentrations resulted in a sustained tachycardia with an attenuation of the depressor effect of i.v. CER and perfusion of GLY solely lowered blood pressure. 5. These results demonstrate that i.v. converting enzyme inhibitor reduces the release of GLU in the RVLM, which was specifically caused by reducing circulating AII, without any effect on GLY release, thus resulting in the reduction of blood pressure with minimal effect on the heart rate.

Anesthesia↗
PubMed1994

Gene expression of the type-1 angiotensin II receptor in rat adrenal gland.

To evaluate the biosynthesis of the type-1 angiotensin II (AT1) receptor and the regulation of AT1 receptor subtypes in the rat adrenal gland, we performed non-radioisotope in situ hybridisation histochemistry with an AT1 receptor complementary RNA (cRNA) probe and a messenger RNA (mRNA) probe. The levels of AT1A and AT1B receptor mRNAs were measured by the reverse transcriptase-polymerase chain reaction method after 4-week treatment with a selective AT1 receptor antagonist, TCV-116, and an angiotensin-converting enzyme inhibitor, delapril. Specific hybridisation signals were observed with the cRNA probe in both the cortex and medulla of the rat adrenal gland. An especially strong signal was observed in the zona glomerulosa. TCV-116 did not affect the levels of expression of AT1A and AT1B receptor mRNAs in the adrenal gland. Delapril, on the other hand, significantly reduced the levels of expression of AT1A and AT1B receptor mRNAs. These results indicate that the sites of biosynthesis of the AT1 receptor are mainly distributed in the adrenal zona glomerulosa. The observed differences in levels of expression of AT1 receptor mRNAs following treatment with TCV-116 and delapril suggest the involvement of the AT2 receptor in the regulation of AT1 receptor subtypes.

Adrenal Glands↗
PubMed1993

Angiotensin blockade and the progression of renal damage in the spontaneously hypertensive rat.

The pathophysiological role of angiotensin II in the development of renal sclerosis was investigated in 5/6-nephrectomized, 12-week-old male spontaneously hypertensive rats. After 1 week of a control period, nephrectomized rats received one of the following treatments for 4 weeks: the selective nonpeptide angiotensin II type 1 receptor antagonist TCV-116 (1 mg/kg per day), the angiotensin converting enzyme inhibitor delapril (30 mg/kg per day), hydralazine (15 mg/kg per day), or vehicle. Urinary protein and albumin excretions and systolic blood pressure were determined every week. Rats with reduced renal mass treated with vehicle had a poor survival rate (30%). Although TCV-116, delapril, and hydralazine treatment significantly improved the survival rate for 4 weeks, hydralazine failed to improve proteinuria and albuminuria as well as the decline in renal function compared with delapril or TCV-116. Histological examination revealed that both TCV-116 and delapril protected glomeruli from sclerosis, whereas hydralazine did not improve histological findings (5%, 7%, and 30% of glomeruli were affected, respectively). These results indicate that angiotensin II plays a dominant role through its type 1 receptor in the pathogenesis of renal deterioration by hypertension.

Albuminuria↗
PubMed1993

Evaluation of orthostatic hypotension using power spectral analysis.

To evaluate the pathogenesis of orthostatic hypotension, we studied the autonomic regulation system by measuring heart rate variability during 60 degrees passive head-up tilt using power spectral analysis in 21 patients with orthostatic hypotension (mean age 62 +/- 2 years, five with histories of cerebrovascular accidents, five with Parkinsonism, five with diabetes mellitus, three with pheochromocytoma, and three with unknown causes) and 15 normal healthy subjects as a control (mean age 63 +/- 2 years). We also assessed plasma epinephrine and norepinephrine response to tilt. During tilt, control subjects showed an increase in heart rate with no change in blood pressure. Spectral analysis of heart rate variability demonstrated increases in the low frequency band (LFB, mainly sympathetic) and low frequency band/high frequency band ratio (LFB/HFB, sympatho-vagal balance). All patients with orthostatic hypotension showed a significant reduction in blood pressure with an increase in heart rate. In patients with histories of cerebrovascular accidents and with Parkinsonism, LFB and the LFB/HFB ratio did not increase. However, in other patients with orthostatic hypotension, LFB and the LFB/HFB ratio increased during tilt. Norepinephrine increased in control subjects and in patients with diabetes mellitus, pheochromocytoma, and unknown causes. In contrast, patients with histories of cerebrovascular accidents and patients with Parkinsonism showed no increase in norepinephrine. Epinephrine responses paralleled those of norepinephrine, but the changes were not significant. Thus, neurological response to tilt is not uniform in patients with orthostatic hypotension. Patients with histories of cerebrovascular accidents and patients with Parkinsonism may have impaired function of central neural mechanisms controlling blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1992

Hypotensive effect associated with a phospholipase C-delta 1 gene mutation in the spontaneously hypertensive rat.

To identify the genes responsible for blood pressure in the spontaneously hypertensive rat strain, we performed a cosegregation analysis between the genotype and blood pressure in a set of male F2 rats obtained by crossmating SHR with Wistar-Kyoto rats, a parental normotensive strain. Our investigation revealed that the phospholipase C-delta 1 polymorphism, which resulted in missense mutation, cosegregates with the lower blood pressure in SHR, and that PLC-delta 1 gene is located on chromosome 8. On the other hand, we found the lack of cosegregation between blood pressure and the nerve growth factor receptor gene, which is linked to a hypertensinogenic gene locus (denoted as BP/SP-1) on chromosome 10. We propose that PLC-delta 1 gene itself of closely linked gene on chromosome 8 is a new candidate with the hypotensive effect, and that BP-SP1 locus does not directly contribute to blood pressure elevation in original SHR.

Animals↗
PubMed1992

Spectral change in heart rate variability in response to mental arithmetic before and after the beta-adrenoceptor blocker, carteolol.

Spectral analysis of heart rate fluctuation was evaluated before and after administration of carteolol, a non-selective beta-adrenoceptor-blocker, to investigate the neural regulatory mechanisms underlying the haemodynamic changes induced by mental stress. Mental stress increased blood pressure and heart rate, with an increased low frequency band, and low frequency/high frequency ratio of the power spectral analysis which are indices of sympathetic activity. Carteolol did not change basal and pre-mental stress measurements of blood pressure, heart rate and spectral density. However, carteolol altered the response to mental stress with a decrease in spectral density of the low frequency band and low frequency/high frequency ratio, and an increase in the high frequency component. These results confirm that mental stress elevates blood pressure by activating the sympathetic nervous system, and suggest that blockade of the beta-adrenoceptor attenuates the pressor response by preventing the autonomic responses to mental stress.

Blood Pressure↗
PubMed1992

Peripheral and central angiotensin II regulates expression of genes of the renin-angiotensin system.

We investigated whether angiotensin (ANG) II has the potential to regulate expression of genes of the renin-angiotensin system (RAS) in peripheral and central tissues. ANG II (0.1 or 6.0 nmol/h) was infused by osmotic minipump into male Sprague-Dawley rats (225-250 g) for 5 days, either intravenously or intracerebroventricularly. We measured angiotensinogen mRNA in liver, adrenal glands, and brain (hypothalamus and lower brain stem), renin mRNA in the kidney, and angiotensin-converting enzyme (ACE) mRNA in the lung and testis by Northern blot analysis. We demonstrated that plasma ANG II increases the levels of liver angiotensinogen mRNA, decreases kidney renin mRNA, and decreases lung ACE mRNA. Intracerebroventricular administration of ANG II resulted in a different pattern of responses of the peripheral RAS components. Liver angiotensinogen mRNA was increased, and kidney renin mRNA was decreased by both doses of ANG II, whereas lung ACE mRNA remained unresponsive at either dose. Centrally mediated influences of ANG II are most likely indirect since plasma ANG II concentration was not changed. This study has revealed that ANG II has profound diverse effects that influence the regulation of its formation. Further, results indicate that genes of the RAS responded to exogenous ANG II in both tissue- and route-specific ways.

Angiotensin II↗
PubMed1991

Angiotensin-(1-7). A member of circulating angiotensin peptides.

We measured the concentrations of three principal products of the renin-angiotensin system and seven of their metabolites in the plasma of anesthetized normal dogs and in dogs 24 hours after bilateral nephrectomy. The levels of the angiotensin peptides were measured by high-performance liquid chromatography combined with radioimmunoassay using three specific antibodies that recognized different epitotes in the sequences of angiotensin I, angiotensin II, and angiotensin-(1-7). The analysis revealed that angiotensin-(1-7) is present in the plasma of intact (4.9 +/- 2.2 fmol/ml) and nephrectomized (0.5 +/- 0.5 fmol/ml) dogs. An intravenous injection of purified hog renin (0.01 Goldblatt unit/kg) increased plasma levels of angiotensin I, angiotensin II, and angiotensin-(1-7) both before and after nephrectomy. These changes were associated with parallel increases in the concentrations of fragments of the three parent peptides. Administration of MK-422 led to the disappearance of circulating angiotensin II and its fragments both before and after a second injection of the same dose of renin. In contrast, MK-422 augmented the plasma levels of both angiotensin I and angiotensin-(1-7). The concentrations of these two peptides, but not the blood pressure, were again augmented by a second injection of renin given after blockade of converting enzyme. These effects were observed both before and after bilateral nephrectomy. These findings show that angiotensin-(1-7) circulates in the blood of normal and nephrectomized dogs. In addition, we found that angiotensin-(1-7) is generated in the blood from the cleavage of angiotensin I through a pathway independent of converting enzyme (EC 3.4.15.1).

Angiotensin I↗
PubMed1991

Importance of the sympathetic nervous system in blood pressure elevation by subpressor intraventricular NaCl and angiotensin II in the rat.

The present study was performed to examine the effect of chemical sympathectomy with guanethidine on the BP change and humoral factors in rats which received continuous and concomitant infusion of i.c.v. hypertonic NaCl with i.v. Ang II, both at subpressor doses for 7 days. Male rats were divided into 3 groups which received the following infusions using an osmotic minipump at a rate of 1 microliter/min: Group 1 (n = 11), 0.15 M NaCl i.c.v. and Ang II (5.4 pmol/kg/min) i.v.; Group 2 (n = 9), 0.8 M NaCl i.c.v. and Ang II i.v.; Group 3 (n = 5), 0.8 M NaCl i.c.v. and Ang II i.v. with daily i.p. injection of guanethidine (40 mg/kg). Significant increase in BP was observed only in Group 2 (from 103 +/- 3 mmHg to 132 +/- 5 mmHg on day 7, p less than 0.001). Addition of i.p. guanethidine to i.c.v. infusion of 0.8 M NaCl and the subpressor dose of Ang II completely prevented increase in the BP, suggesting that the presence of the intact sympathetic nervous system is necessary for the development of BP elevation in response to i.c.v. hypertonic NaCl plus i.v. Ang II. Thus, the sodium status in the central nervous system is important in the regulation of BP and is closely related to the activity of the sympathetic nervous system.

Angiotensin II↗
PubMed1990

Differential blood pressure responses to oral and central salt administration in two substrains of Dahl rats.

Studies were made on whether oral or intraventricular (icv) NaCl had different effects on the blood pressure (BP) of Dahl rats. Five groups of each strain of Dahl rats, salt-sensitive (S) and salt-resistant (R) rats, were given, respectively, a diet containing 0.3% and icv infusion of 0.15 mol/L NaCl (group 1, control group) or 0.8 mol/L NaCl (group 2), a diet containing 8% NaCl and icv infusion of 0.15 mol/L (group 3) or 0.8 mol/L NaCl (group 4) for 12 days, or an 8% NaCl diet and icv infusion of 5% glucose (group 5). The icv infusions were made into the third cerebral ventricle with an osmotic minipump. In the control group of S rats (group 1) the BP was 120 +/- 4 mm Hg, whereas the BP in groups 3, 4 and 5 were 154 +/- 4, 161 +/- 5 and 153 +/- 3 mm Hg, respectively, and that in group 2 was 142 +/- 3 mm Hg on day 12. In the R rat, group 2 and group 4 showed a significant increase in BP over that of the control group. Multivariate analysis (quantification I) of these data confirmed that the BP of S rats was more sensitive to oral salt loading and that of the R rat was more strongly influenced by central salt administration. These results indicate that the two substrains of Dahl rats show different BP responses to oral and central administrations of NaCl.

Animals↗
PubMed1990

Haemodynamic effect of endothelin, a novel potent vasoconstrictor in dogs.

1. The effects of endothelin (40 and 400 pmol/kg, intravenous (i.v.), a novel vasoconstrictor, on haemodynamics were evaluated in normal dogs and dogs treated with hexamethonium. 2. The lower dose of endothelin caused no significant changes in mean blood pressure (MBP), heart rate (HR), cardiac output (CO), or total peripheral resistance (TPR) in normal dogs. In dogs treated with hexamethonium MBP decreased transiently associated with decrease in TPR. 3. In both dogs, the higher dose of endothelin caused MBP increase with CO increase in an early phase, and with TPR increase in a later phase. In normal dogs, the CO decreased 60 min after endothelin, but in dogs treated with hexamethonium the decrease in CO was not significant. 4. Electrocardiograms showed ST changes and arrhythmias. 5. Thus, endothelin has dual effects on both the vasculature and the heart, its effect depending on its dose and the time after its administration: initial vasodilation followed by prolonged vasoconstriction, and cardiostimulation followed by cardiosuppression. The cardiosuppression appears to be mediated in part by a neural mechanism.

Animals↗
PubMed1990

Effect of aspirin on the pressor activity of endothelin.

To examine the inhibition of prostaglandins to the pressor activity of endothelin, hemodynamic changes of dogs pretreated with aspirin in response to endothelin were compared with those of control. In control dogs, endothelin rose blood pressure due to vasoconstriction, with a transient vasodilation in some dogs in the initial phase. In dogs treated with aspirin, the initial vasodilation and the subsequent vasoconstriction were also noted, but the zenith of the total peripheral resistance was observed earlier, compared with control dogs. Thus, prostaglandins do not appear to have a role in the initial vasodilatory action of endothelin, but may modify the long lasting vasoconstriction in the late phase.

Animals↗
PubMed1990

Effect of the calcium antagonist nicardipine on the pressor action of endothelin.

To evaluate hemodynamic actions of endothelin, anesthetized normal dogs and dogs with two doses of nicardipine received endothelin (400 pmol/kg, i.v.). Normal dogs showed an increase in blood pressure (BP) associated with an early (5 min) increase in cardiac output (CO) and a later (60 min) increase in total peripheral resistance (TPR). The lower dose of nicardipine (0.01 mg/kg/h) abolished the latter vasoconstrictive BP elevation. Dogs with the higher dose of nicardipine (0.1 mg/kg/h) did not show any changes in BP, CO or TPR. Thus, endothelin has both cardiostimulatory and vasoconstrictive actions, depending on the degree of calcium influx.

Animals↗