Search PubMed⌕ Search

Biomedical subjects

H Mikami

Publications and source records attributed to H Mikami.

At least 181 records · Page 10Linked to original sources
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

Absence of nocturnal fall in blood pressure in elderly persons with Alzheimer-type dementia.

Circadian changes of the blood pressure and heart rate in elderly normotensive bedridden patients with severe dementia of the Alzheimer type (group D) were compared with those in elderly normotensive bedridden patients without dementia (group R), normotensive subjects with normal daily activity (group N), and hypertensive patients with normal daily activity (group H). In groups R, N, and H, the blood pressure increased in the afternoon and decreased at midnight; in group D, however, although it increased in the afternoon, it did not decrease at night. The circadian changes of the heart rate were similar in all four groups, showing maxima in the afternoon and minima at midnight. Thus, a specific alteration was found in the circadian rhythm of the blood pressure in patients with Alzheimer-type dementia.

Activities of Daily Living↗
PubMed1990

Effects of endothelin on neuroeffector junction in mesenteric arteries of hypertensive rats.

The effect of endothelin, a novel vasoconstrictor peptide, on the adrenergic neuroeffector junction was investigated in isolated perfused mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The vasoconstrictor responses to periarterial sympathetic nerve stimulation and exogenous norepinephrine were determined. Infusion of endothelin-1 increased the baseline perfusion pressure dose dependently to similar extents in the two strains. A subpressor dose of endothelin-1 (10(-10) M) enhanced the pressor response to norepinephrine; its effect was greater in WKY rats than in SHR. Endothelin-1 (10(-12) to 10(-10) M) attenuated the pressor response to sympathetic nerve stimulation, and the degree of inhibition tended to be less in SHR than in WKY rats. Higher doses (3 x 10(-10) and 10(-9) M) of endothelin-1 enhanced the pressor response to nerve stimulation in both WKY rats and SHR. Endothelin-1 inhibited norepinephrine release from rat mesenteric arteries; the inhibition was significantly less in SHR than in WKY rats. These results suggest that endothelin enhances the responsiveness of alpha-adrenergic receptors to catecholamines, whereas it inhibits presynaptic adrenergic neurotransmission. Thus, endothelin can interact with the neuroeffector junction in addition to having a vasoconstricting effect in peripheral vessels. The difference in the mode of modulation by endothelin at the vascular neuroeffector junction in SHR from that in WKY rats might explain the maintenance of hypertension.

Animals↗
PubMed1990

Strain differences in guinea pigs' bronchial sensitivity to acetylcholine.

The bronchial sensitivity to acetylcholine (ACh) of guinea pigs of various strains was investigated to clarify strain differences. Inbred Strain 2, Strain 13 and JY-1 and non-inbred Hartley strain (two colonies) were used in this experiment. (1) Guinea pigs were exposed to 0.08% ACh aerosol and the time needed to produce falling down (TNPFD) was determined. Mean +/- standard error of TNPFD (n = 14 per group) of animals was 182 +/- 28 sec, 148 +/- 22 sec, 210 +/- 30 sec, 342 +/- 24 sec and 406 +/- 36 sec in Strain 2, Strain 13, JY-1, Hartley (Japan SLC) and Hartley (Hitachi), respectively. There was a significant difference in TNPFD between inbred strains and non-inbred strains (P less than 0.05 or P less than 0.01), indicating that inbred strains had higher sensitivity. (2) Guinea pigs were exposed to 20-5000 micrograms/ml ACh for 2 min. The mean dose threshold as determined by transcutaneous oxygen pressure was 524 micrograms/ml, 424 micrograms/ml, 614 micrograms/ml, 1317 micrograms/ml and 1651 micrograms/ml (n = 14 per group) in Strain 2, Strain 13, JY-1, Hartley (Japan SLC) and Hartley (Hitachi), respectively. Inbred strains showed lower dose thresholds than non-inbred strains. (3) Isolated trachea-lungs of 5 guinea pigs were perfused with 10(-9)-10(-5) g/ml ACh to determine strain differences. Dose response curves of animals of inbred strains shifted to the left (lower concentrations), unlike those of non-inbred strains, suggesting that inbred strains had higher sensitivity to ACh than non-inbred strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

[Circadian changes of blood pressure in the elderly with Alzheimer's type dementia].

We evaluated the circadian changes of blood pressure in the elderly with Alzheimer's type dementia with ambulatory blood pressure monitoring (ABPM-630, Nihon Colin, Aichi, Japan). Blood pressure and heart rate were high in the daytime and low in the nighttime in the elderly without dementia. Blood pressure did not decrease in the nighttime in the elderly with dementia, although heart rate decreased. Thus, the circadian rhythm of blood pressure was selectively impaired in the elderly with Alzheimer's type dementia.

Aged↗
PubMed1990

Increased plasma level of endothelin with vasoconstriction after dextran infusion.

Our previous study demonstrated that volume expansion with dextran produced blood pressure elevation due to vasoconstriction 3 hours after the cessation of infusion. To examine whether endogenous endothelin contributes to this vasoconstriction, we measured plasma level of endothelin before, immediately after, and 3 hours after the administration of dextran. Plasma level of endothelin decreased immediately after the administration (from 1.5 +/- 0.3 pg/ml to 1.1 +/- 0.2 pg/ml, P less than 0.05), and increased 3 hours after the administration (2.1 +/- 0.3 pg/ml, P less than 0.05). However, the changes in the plasma level of endothelin did not significantly correlated with those in blood pressure or total peripheral resistance. Thus, vasoconstriction after dextran infusion was accompanied by an increase in the plasma level of endothelin, but further evaluation is needed for the direct role of this peptide in the vasoconstrictive blood pressure elevation.

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↗
PubMed1990

[Pathogenesis and treatment of hypertension].

Many hypotheses have been advocated to explain the pathogenesis of essential hypertension: Guyton's autoregulation theory, the natriuretic hormone theory represented by de Wardner, the sympathetic nervous system theory, and the genetic theory etc. However, none of these theories alone explain the single etiology of hypertension and as stated in Page's Mosaic theory, complicated interaction of many factors has been implicated. We have performed a series of studies to evaluate the interaction between the pressor and depressor systems in relation to salt balances and found in general that hyperfunction of the pressor system and the reduced activity of the depressor systems exist in essential hypertension. Many substances also have been found to be involved in the blood pressure regulation and recently endothelin, a most potent pressor peptide which derives from endothelial cell, was discovered and synthesized by Yanagisawa et al. and its pathophysiological roles are now being extensively investigated. On the other hand, the development of many antihypertensive drugs with different modes of action has enabled us to individualize the treatment of hypertension. Further development of drugs with fewer adverse side effects, whether symptomatic or of abnormality in the clinical laboratory data, and which can maintain or even improve the quality of life is mandatory to pursue life-long treatment of hypertension for successful prevention of the fatal vascular complications.

Antihypertensive Agents↗
PubMed1990

Endothelin activates the vascular renin-angiotensin system in rat mesenteric arteries.

The effects of endothelin on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries by measuring vascular renin activity and angiotensin II released into the perfusate. Infusion of endothelin (10(-9)M and 10(-11)M) increased the vascular renin activity and angiotensin II release. Pretreatment with nicardipine (10(-6)M), a calcium channel blocker, significantly suppressed these effects of endothelin. These results suggest that endothelin activates the vascular renin-angiotensin system via intracellular calcium metabolism. Vascular angiotensin II produced by endothelin may modulate the local effect of endothelin on the resistance vessels.

Angiotensin II↗
PubMed1989

Endothelin inhibits presynaptic adrenergic neurotransmission in rat mesenteric artery.

The effect of endothelin(ET) on adrenergic neurotransmission was examined in isolated perfused rat mesenteric arteries. Porcine ET(10(-12) to 10(-10)M) attenuated the pressor response to sympathetic nerve stimulation (NS). It also stimulated the release of prostaglandin E2 (PGE2), but its inhibition of the pressor response to NS was not affected by indomethacin treatment. ET also caused dose-dependent inhibition of [3H]norepinephrine release during NS. Higher doses of ET rather enhanced the pressor response to NS. These results suggest that ET inhibits presynaptic adrenergic neurotransmission without mediation of PGE2, while it potentiates the responsiveness of the postsynaptic alpha-adrenergic receptor. Thus ET appears to act directly on the neuroeffector junction as well as on the peripheral vasculature.

Adrenergic Fibers↗
PubMed1989

Endothelin stimulates the release of prostacyclin from rat mesenteric arteries.

The effect of endothelin on the release of prostacyclin was examined in perfused rat mesenteric arteries with or without their pretreatment with indomethacin. Porcine endothelin at 10 pmol (a subpressor dose) and 40 pmol stimulated the release of 6-keto-PGF1 alpha, a stable metabolite of prostacyclin. Rat endothelin also stimulated its release, but less than porcine endothelin. Pretreatment with indomethacin completely inhibited this 6-keto-PGF1 alpha release. These results indicate that endothelin stimulates the release of prostacyclin from mesenteric arteries. This release may modulate the action of endothelin locally.

Animals↗
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

Effect of chronic renal failure on the level of albumin messenger RNA.

The effects of chronic renal failure on the level of albumin mRNA and the transcription rate of the albumin gene were studied in seven of eight nephrectomized rats. A paired feeding procedure was employed to eliminate a nutritional difference between sham-operated control and uremic rats. Total RNA was isolated from the livers of control and uremic rats fasted for 24 or 48 hours. The mRNA level was measured by RNA-cDNA dot blot hybridization, and the transcription rate was measured by the "run-on" transcription assay in isolated nuclei. The albumin mRNA levels in uremic rat livers were reduced to 75% at the 24-hour fasted state, and to 45% at 48-hour fasted state compared with those in the respective control groups. There was no difference in the level of beta-actin mRNA between these groups. However, there was no difference in the transcription rate of the albumin gene between control and uremic rats. Northern analysis showed that albumin mRNA isolated from uremic rat liver was identical in size with that from the control. These results suggested that a posttranscriptional process, involving the destabilization of cytoplasmic mRNA, is responsible for the uremia-induced repression of albumin synthesis.

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↗