Katsutoshi Katahira

Converting enzyme inhibitors regressed cardiac hypertrophy and reduced tissue angiotensin II in spontaneously hypertensive rats

To examine the role of the tissue renin-angiotensin system in left ventricular hypertrophy, converting enzyme inhibitors were administered orally to 12-week-old male spontaneously hypertensive rats (SHR) for 4 weeks, and cardiac tissue angiotensin II was measured. Treatment with enalapril (10 mg/kg per day) and trandolapril (1 mg/kg per day) lowered systolic blood pressure, left ventricular weight and left ventricular angiotensin II content. Plasma angiotensin II concentration was increased by the treatment with enalapril whereas trandolapril did not cause any change. There was significantly positive correlation between left ventricular weight and angiotensin II content. Because angiotensin II promotes cell proliferation, these results suggest that cardiac tissue angiotensin II, rather than circulating angiotensin II, may account for the pathophysiology of left ventricular hypertrophy in SHR.

Significant increase in plasma immunoreactive atrial natriuretic polypeptide concentration during head-out water immersion

To investigate the physiological regulatory mechanism of human atrial natriuretic polypeptide (hANP) secretion, plasma hANP was measured by a direct radioimmunoassay during head-out total body water immersion (WI) in normal men. Five healthy men were immersed in water for 1 hr. Urine volume and Na excretion were significantly increased during WI. Plasma hANP increased significantly during WI peaking at 30 min. and returned toward the baseline after WI. Plasma renin activity and norepinephrine were suppressed occasionally during WI. Plasma ADH did not change throughout the study period. Maximal increments in plasma hANP correllated with that in urine output or urinary Na excretion during WI. These data suggest that acute central hypervolemia caused by WI increases hANP secretion and that this increase may participate in the diuretic response to WI.

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-selectiveβ-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 theβ-adrenoceptor attenuates the pressor response by preventing the autonomic responses to mental stress.

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.

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.

Amino acids in the medulla oblongata contribute to baroreflex modulation by angiotensin II

We investigated the underlying mechanisms of baroreflex alteration produced by intravenous angiotensin II (ANG II) by monitoring the release of amino acids from the rostral ventrolateral medulla (VLM) using a brain microdialysis technique. Reflex changes in heart rate were elicited by bolus intravenous injection of phenylephrine (2-40 micrograms/kg) before and 120 min after the initiation of administration of a subpressor dose of ANG II (5.4 pmol/kg/min) or vehicle. The slope of the regression line obtained from changes in mean arterial pressure and heart rate elicited by phenylephrine was used as an index of baroreceptor reflex sensitivity. ANG II administration for 120 min significantly attenuated the baroreflex sensitivity (from -0.59 +/- 0.10 to -0.30 +/- 0.08 bpm/mmHg). This attenuation was accompanied with an increase in the release of glutamate and glycine from the VLM (+40% and +20%, respectively) at 120 min. Glycine perfusion into this area resulted in an attenuation of baroreflex sensitivity with a magnitude similar to that obtained with infusion of a subpressor dose of ANG II, whereas glutamate perfusion caused a resetting of baroreflex. These results suggest that glycine and glutamate are involved in cardiovascular regulation in the VLM. Furthermore, the augmented releases of these amino acids may account for the underlying mechanism of ANG II-induced attenuation of baroreflex function.

EFFECT OF LONG‐TERM TREATMENT WITH AN ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR ON THE RENIN‐ANGIOTENSIN SYSTEM IN SPONTANEOUSLY HYPERTENSIVE RATS

1. To obtain information on regulation of the brain renin–angiotensin system, the effect of long‐term administration of angiotensin‐converting enzyme (ACE) inhibitor on brain renin and angiotensinogen mRNA was studied.

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

In a search for factors contributing to the sustained Mood pressure (BP) elevation in acutely volume-loaded animals, dextran dissolved in lactated Ringers solution (20 ml/kg) was infused into 34 mongrel dogs over a period of 1 hour under pentobarbital anesthesia and changes in bemodynamic 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 natriuretk factor, urine volume, and urinary sodium excretion were identical in the two groups, and natrluresis 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 natriuretk factor plays a role in the resistance-dependent BP elevation. The mechanism and physiological importance of hypersensitivity to vasoactive substances remain to be elucidated.

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.

Effect of cromakalim (BRL 34915) on hemodynamic and electrocardiographic changes induced by endothelin in dogs

SummaryWe evaluated whether cromakalim (BRL 34915), a vasorelaxant agent which acts by opening potassium channels, could affect the systemic effects of endothelin, a newly discovered vasoconstrictive peptide. Intravenous administration of endothelin alone (400 pmol/kg) to anesthetized dogs produced blood pressure elevation, which was associated with an increase in cardiac output in the early phase, and was associated with an increase in total peripheral resistance in the late phase. Electrocardiogram showed significant ST-elevation in II, III, and aVL, and ST-depression in a VR and aVL. The same dose of endothelin given to dogs pretreated with cromakalim did not induce these hemodynamic and electrocardiographic changes. Thus, cromakalim, a potassium activator, inhibited the hemodynamic and electrocardiographic actions of endothelin, suggesting that hyperpolarization due to potassium channel activation inhibited the voltage-dependent calcium channel, which is thought to be a major mechanism for the pressor action of endothelin.