Kazuoki Kondo

Serum uric acid and the renin-angiotensin system in hypertension.

To study whether the renin‐angiotensin system is related to hyperuricemia in hypertension, the serum concentration of uric acid was determined in 96 patients with various types of hypertension and various degrees of plasma renin activity (PRA). In malignant hypertension, both PRA and the serum uric acid level were higher than in essential hypertension; but in primary aldosteronism or desoxycorticosterone‐excess hypertension, they were lower than in the essential type. In renovascular hypertension, PRA was higher than in essential hypertension, but the serum uric acid levels were similar. There were no differences in PRA and serum uric acid concentration between Cushings syndrome and essential hypertension. The serum uric acid level in high‐renin essential hypertension was higher than in either the normal‐renin or the low‐renin type. There was a significant correlation between serum uric acid concentration and PRA in the basal state, and between the change in PRA and the change in serum uric acid induced by administration of furosemide. Apparently the close correlation between the renin‐angiotensin system and the concentration of serum uric acid is related to changes in extracellular fluid volume, although an intrarenal effect of angiotensin II cannot be excluded.

SQ 14, 225 attenuates the vascular response to norepinephrine in the rat mesenteric arteries

Abstract SQ 14, 225, a new angiotensin-converting enzyme inhibitor, attenuated the vascular contraction induced by norepinephrine in the perfused rat mesenteric vascular bed, while SQ 20, 881, an another converting enzyme inhibitor, did not have any effect on the vascular reactivity. Furthermore, this effect of SQ 14, 225 was not altered in the presence of bradykinin or angiotensin II in the perfusate. These results suggest that SQ 14, 225 may have a direct antihypertensive effect which is not mediated by the inhibition of angiotensin-converting enzyme.

Central and peripheral effects of bradykinin and prostaglandin E2 on blood pressure in conscious rats

SummaryBradykinin or prostaglandin E2 (PGE2), when injected intravenously, decreased blood pressure of conscious rats in a dose-dependent manner, while intracerebroventricular injections of bradykinin or PGE2 caused a dose-dependent increase in blood pressure. SQ 14,225, an inhibitor of angiotensin converting enzyme, potentiated the central pressor or peripheral depressor effect of bradykinin. Indomethacin, an inhibitor of prostaglandin synthesis, almost completely inhibited the central pressor effect of bradykinin when injected intraventricularly. Indomenthacin, when injected intravenously, failed to inhibit the peripheral depressor effect of bradykinin, whereas it significantly attenuated the peripheral depressor effect of bradykinin when the angiotensin converting enzyme was inhibited with SQ14,225. These results suggest that the central pressor effect of bradykinin is mainly mediated by the synthesis of prostaglandins in the central nervous system, while only a small fraction of peripheral depressor effect of bradykinin is, at least in conscious rats, mediated by the synthesis of prostaglandins in the systemic circulation.

Effects of intracerebroventricular administration of prostaglandins I2, E2, F2α and indomethacin on blood pressure in the rat

The effects of intraventricularly administered prostaglandins I2 (PGI2), E2 (PGE2), F2alpha (PGF2 alpha) and indomethacin on systemic blood pressure were investigated in conscious rats. PGI2 (1.25--10 micrograms/kg) decreased blood pressure in a dose-related manner, whereas PGE2 (100--1000 mg/kg) dose-dependently increased blood pressure. Both PGF2 alpha (0.31--20 micrograms/kg) and indomethacin (0.625--40 micrograms/kg) had no effects on blood pressure. These results indicate that intraventricular injection of PGI2 or PGE2 can induce significant changes in blood pressure, while endogenous prostaglandins synthesized in the brain seem to play a minor role in direct regulation of systemic blood pressure in the rat.

Effects of prostaglandins E2 and I2, and arachidonic acid on vascular reactivity to norepinephrine in isolated rat mesenteric artery, hind limb and splenic artery

The effects of prostaglandins E2 (PGE2) and I2 (PGI2), arachidonic acid, and indomethacin on the vascular reactivity to norepinephrine were tested in three different isolated rat vascular beds (mesenteric artery, hind limb and splenic artery) perfused with the Krebs bicarbonate solution. In these vascular beds PGE2 (0.25--16 ng/ml), PGI2 (0.1--100 ng/ml), arachidonic acid (0.1--10 micrograms/ml) or indomethacin (5--25 micrograms/ml) in the perfusate did not change the basal pressure. In the splenic artery, both PGE2 and PGI2 attenuated the vascular response to norepinephrine in a dose-related manner. In the mesenteric vascular bed and the hind limb, however, PGE2 potentiated the vascular response to norepinephrine, while PGI2 attenuated this response. Acahidonic acid, a prostaglandin precursor, potentiated the vasoconstrictor response to norepinephrine in the mesenteric artery and the hind limb, whereas in the splenic artery, attenuation of the response to norepinephrine occurred. In these three vascular beds, indomethacin, a prostaglandin synthetase inhibitor, attenutated the vascular response to norepinephrine. In the mesenteric artery and the hind limb, PGE2 and not PGI2 reversed the effect of indomethacin, while in the splenic artery, neither PGE2 nor PGI2 reversed the inhibitory effect of indomethacin. These results suggest that, at least in the rat mesenteric artery and the hind limb where the modulating effect of arachidonic acid is similar to that of PGE2, PGE2 and not PGI2 is a primary endogenous prostaglandin in determining the vascular reactivity to norepinephrine.

Effects of prostaglandins E2, I2 and F2α, arachidonic acid and indomethacin on pressor responses to norepinephrine in conscious rats

The effects of prostaglandins E2 (PGE2), I2 (PGI2) and F2 alpha (PGF2 alpha), arachidonic acid and indomethacin on pressor responses to norepinephrine were examined in conscious rats. Intravenously infused PGE2, (0.3, 1.25 micrograms/kg/min), PGI2 (50, 100 ng/kg/min), PGF2 alpha (1.8, 5.4 micrograms/kg/min) and arachidonic acid (0.7, 1.4 mg/kg/min) did not change the basal blood pressure. Both PGE2 and PGI2 significantly attenuated pressor responses to norepinephrine, whereas PGF2 alpha significantly potentiated them. Arachidonic acid, a precursor of the prostaglandings (PGs), significantly attenuated pressor responses to norepinephrine. Since the attenuating effect of arachidonic acid was completely abolished by the pretreatment with indomethacin (5 mg/kg), arachidonic acid is thought to exert an effect through its conversion to PGs. On the contrary, intravenously injected indomethacin (0.2--5.0 mg/kg) facilitated pressor responses to norepinephrine in a dose-related manner without any direct effect on the basal blood pressure. These results suggest that endogenous PGs may participate in the regulation of blood pressure by modulating pressor responses to norepinephrine in conscious rats.

Chronic kidney disease in postmenopausal women

Menopause is derived from the Greek words men (month) and pauses (cessation) and means permanent cessation of menstruation after the loss of ovarian activity. Chronic kidney disease (CKD) has recently been associated with cardiovascular events in several studies. CKD patients have a heavy burden of traditional cardiovascular risk factors in addition to a range of nontraditional risk factors such as inflammation and abnormal metabolism of calcium and phosphate. In this review, the association of CKD and cardiovascular disease (CVD), as well as of osteoporosis in postmenopausal women is discussed. CKD mineral and bone disorder, characterized by disturbances of calcium/phosphate/parathyroid hormone, bone abnormalities and vascular and soft tissue calcification, is highly prevalent in CKD and is a strong, independent predictor of bone fracture, CVD and death. Estrogen has been shown to: (a) decrease the expression of angiotensin type 1 receptors in vasculature and kidneys; (b) reduce the expression and activity of angiotensin-converting enzyme, and (c) cause the release of angiotensinogen substrate from the liver. However, the degree of activation or suppression of the renin–angiotensin–aldosterone system by estrogen has not been clearly established. Clinical data on the effects of estrogen therapy on bone mineral densities are extremely limited in the ESRD population. CVD is the most common cause of death in postmenopausal women with CKD and many contributing factors have been explored. Future research for prevention of CVD in postmenopausal women with CKD would focus on the biology of vascular calcification as well as bone loss.

Effects of angiotensin-converting enzyme inhibitors on the vascular response to norepinephrine

The effects of three types of angiotensin-converting enzyme inhibitor, SQ 14225 (captopril), SQ 20881 (teprotide) and SA 446 (Santen, Osaka, Japan), on the vascular contraction induced by norepinephrine were studied in the perfused rat mesenteric vascular bed. (1) SQ 14225 attenuated in the vascular contraction induced by norepinephrine, but SQ 20881 and SA 446 revealed no effect on vascular reactivity. (2) The effect of SQ 14225 was not altered in the presence of bradykinin or angiotensin II in the perfusate. On the basis of these results it is suggested that the attenuating effect on the vascular response to norepinephrine may be limited to SQ 14225 and that its effect is not mediated through the renin-angiotensin or kallikrein-kinin system.

Effect of prostaglandin E2 on vascular reactivity to norepinephrine in isolated rat mesenteric artery, hind limb and splenic artery

The effects of prostaglandin E2 (PGE2) and indomethacin on the vascular reactivity to norepinephrine were tested in three different isolated rat vascular beds (mesenteric artery, hind limb and splenic artery) perfused with the Krebs bicarbonate solution. In these vascular beds PGE2 (0.1-64 ng/ml) or indomethacin (09.1-96 microgram/ml) in the perfusate did not change the basal pressure. In the mesenteric vascular bed and the hind limb, PGE2 dose-dependently potentiated the vascular response to norephinephrine, whereas PGE2 dose-dependently inhibited the vascular response to norepinephrine in the splenic artery. In these three vascular beds indomethacin in the perfusate dose-dependently attenuated the vascular response to norepinephrine. In the mesenteric artery and the hind limb PGE2 restored the effect of indomethacin, but in the splenic artery PGE2 did not restore the inhibitory effect of indomethacin. These results indicate that the modulating effect of exogenously administrated PGE2 on the vascular action to norepinephrine varies in different vascular beds. It is also suggested that the contribution of endogenous PGE2 synthesized in the vascular wall to the vascular reactivity to norepinephrine is, as well as the effect of exogenous PGE2, different in different vascular beds.

Myotonic dystrophy and hyperthyroidism

The association of myotonic dystrophy and hyperthyroidism is rare. In the first such case in Japan, hyperthyroidism induced severe exacerbation of muscle weakness, which improved when the thyroid disorder was treated.