[Effect of aging on sensitivity of blood pressure to salt].

We investigated the correlation between aging and sensitivity of blood pressure to salt. 88 non-treated essential hypertensives were divided into four groups: less than 40 years old (n = 20), 40-49 years old (n = 20), 50-59 years old (n = 39), and greater than 60 years old (n = 11). Changes of blood pressure, plasma renin activity (PRA), plasma aldosterone concentration (PAC), plasma norepinephrine (PNE), and plasma epinephrine (PE) due to salt load were compared among four groups. Salt sensitivity of blood pressure was increased with aging, and there was a positive correlation between them (r = 0.30, p < 0.01). Decrement of PRA due to salt load was decreased with aging, and there was a negative correlation between them (r = -0.35, p < 0.05). PCA and PNE were suppressed by salt load, and the decrement degrees did not change with age. PE did not change by salt load. We conclude that salt sensitivity is increased with age in essential hypertensives, and renin-angiotensin system might be involved in it.

Role of renomedullary thromboxane A2 in development of doca-salt hypertension.

To clarify the role of renal thromboxane (TX)A2 in the development of deoxycorticosterone acetate (DOCA)-salt induced hypertension, relationship between systolic blood pressure and the synthesis of renal TXA2 was investigated in 18 rats without and with OKY-046 administration which suppressed the synthesis of renal TXA2. Systolic blood pressure was significantly higher in DOCA-salt group than in control and OKY groups. The synthesis of 6-keto-prostaglandin(PG)F1 alpha and TXB2 in both renal arteries and cortical slices were more enhanced in DOCA-salt and OKY groups than in control group, but there was no significant difference between DOCA-salt and OKY groups. In contrast, the synthesis of 6-keto-PGF1 alpha in renomedullary slices did not vary significantly among three groups, and that of TXB2 was more increased in DOCA-salt group than in control and OKY groups. The cumulative sodium retention was significantly greater in DOCA-salt group than in control group. Administration of OKY-046 reduced the cumulative sodium retention in DOCA-salt rats by 45% toward that of the control group. These results might suggest that the enhanced production of renomedullary TXB2 was important to the development of DOCA-salt induced hypertension.

Changes in vascular wall production of prostacyclin and thromboxane A2 in spontaneously hypertensive rats during maturation and the concomitant development of hypertension.

The purpose of this study was to clarify how the metabolism of vascular prostacyclin (PGI2) and thromboxane (TX) A2 in spontaneously hypertensive rats (SHR) is involved in aging and development of hypertension. We removed the aortic walls from 5-week-old and 20 to 25-week-old SHR and age-matched Wistar Kyoto rats (WKY). At 5 weeks of age, there was no significant difference in basal and maximal (arachidonic acid 0.1 mM) 6-keto-PGF1 alpha production between SHR and WKY, but the TXB2 generation in the SHR aortic wall was markedly enhanced as compared with that in WKY. At 20 to 25 weeks of age, the SHR aortic wall synthesized about 1.5 times more 6-keto-PGF1 alpha in the basal condition and twice as much as in the maximal condition as did the WKY wall. However there was no significant difference in TXB2 production between SHR and WKY. Age-dependent increase of vascular 6-keto-PGF1 alpha was greater in SHR than in WKY. Moreover, the maximal/basal 6-keto-PGF1 alpha production ratio increased with age in SHR, but not in WKY. The synthesis of vascular TXB2 was enhanced with age in WKY, but did not change with age in SHR. These data suggest that not only the enhanced basal generation of vascular 6-keto PGF1 alpha but also a much greater reservoir of 6-keto-PGF 1 alpha synthesis in SHR was induced by both hypertension and maturity. The increased production of vascular TXB2 in young SHR may affect the development of hypertension.