The F1 hybrids (F1) of spontaneously hypertensive rats (SHR) and Wistar rats (W), whose kidneys were transplanted from SHR at the age of 10 weeks and 20 weeks, showed significant elevation of blood pressure (BP) for 11 weeks after the transplantation. In F1 with W or F1 kidneys BP was decreased near to the normal level. F1 whose kidneys were transplanted from SHR or W showed low renin activity both in plasma and the kidney. It is suggested that BP of SHR is probably determined by the renal pro-hypertensive factor(s) other than renin influencing on sympathetic nerves through central nervous systems.

Plasma and kidney renin activities (PRA, KRA) were determined in male spontaneously hypertensive rats (SHR), the inbred strain of F27-30. Blood samples of 0.5 ml for PRA determination were obtained through a cannula inserted into the abdominal aorta without anesthesia to minimize renin release from the kidney. The PRA was 30 wk. The KRA of SHR at age 10, 20, and 30 wk was also lower, confirming a previous report. At 5 wk of age, KRA was slightly higher than that of normal controls. At 50 wk of age, PRA and KRA were significantly lower in SHR (F25) from a random-bred colony than in normal Donryu rats. It is suggested that the renin-angiotensin system is suppressed in SHR as a compensatory reaction against blood pressure elevation.

1 The haemodynamic, antianginal and antihypertensive effects of nicardipine, a vascular selective calcium antagonist, were studied in experimental animals. 2 In the canine isolated coronary artery, nicardipine relaxed potassium-induced contraction and suppressed 3,4-diaminopyridine-induced rhythmic contractions more effectively than nifedipine, verapamil or diltiazem. 3 In anaesthetised rats, nicardipine prevented the elevation of ST segment induced by intracoronary injection of methacholine. 4 In anaesthetised dogs, nicardipine produced a greater vasodilatation in vertebral, carotid, and coronary vessels than in mesenteric, femoral, and renal vessels and did not affect myocardial oxygen consumption. 5 In conscious monkeys, nicardipine given intravenously lowered blood pressure and gave rise to reflex tachycardia but did not prolong the A-V conduction time. 6 Nicardipine given orally lowered blood pressure in spontaneously hypertensive rats (SHR), renal hypertensive rats (RHR), and deoxycorticosterone acetate/salt hypertensive rats (DOCA/Salt), as well as in normotensive rats. 7 Long-term treatment with nicardipine given orally for 12 weeks effectively lowered high blood pressure in the three types of hypertensive rats, reduced cardiac hypertrophy in SHR and DOCA/Salt rats, and prevented mortality from stroke in DOCA/Salt rats. Combined treatment with nicardipine and af,-adrenoceptor blocking agent (indenolol) showed an antihypertensive effect similar to that obtained with nicardipine alone. 8 Conscious renal hypertensive dogs given repeated oral administration of nicardipine for 14 days did not develop tolerance to the hypotensive activity of nicardipine. Under the same conditions, tolerance to hydralazine developed within 4 days.Keywords antianginal effect antihypertensive effect calcium antagonist cardiovascular effect nicardipine

Plasma and kidney renin activity (PRA, KRA) were determined in the spontaneously hypertensive (SHR) rats, the stroke-resistant and -prone substrains (SHRSR, SHRSP) from 5 to 30 weeks of age. Results were compared with those of two normotensive strains, Wistar-Kyoto (WKY) and Donryu (DON) rats. PRA in the SHRSP at 20 and 30 weeks of age were significantly increased when compared to other strains of rats (P < 0.01). In SHRSP rats at these ages, blood pressure exceeded the critical level of 220 mmHg and cerebral lesions were observed in 41% at autopsy. There were no significant differences in PRA among other hypertensive and normotensive strains. KRA in three substrains of the SHR were normal or subnormal as compared to WKY and DON rats. These results indicate that a direct role of the renin-angiotensin system in the SHR and its substrains can be excluded in the initiation and the maintenance of hypertension. However, the activated renin-angiotensin system in SHRSP rats in the course of malignant hypertension at 20 weeks of age and later, could participate in raising blood pressure above the levels of the SHR and SHRSR. Considering out data and others, there are many similarities in renin profile between the SHR and its two substrains, and human essential hypertension in which PRA can be classified as low, normal or high.

YM-12617, 5-[2-[[2-(2-ethoxyphenoxy)ethyl]-amino]propyl]-2 -methoxybenzenesulfonamide HCl is a structurally new type of extremely potent alpha 1-adrenoceptor antagonist. Its alpha-adrenoceptor blocking properties have been compared with those of prazosin, phentolamine and yohimbine using both pharmacological and 3H-ligand binding techniques in vitro and in vivo. In the isolated rabbit aorta, a tissue known to contain mainly alpha 1-adrenoceptors at postjunctional sites, YM-12617 competitively antagonized noradrenaline-induced contraction with a pA2 value of 10.11. Although YM-12617 was also a competitive antagonist toward clonidine at prejunctional alpha 2-adrenoceptors in the isolated rat vas deferens, its affinity for these receptors (pA2 = 6.41) was 5,000 times lower than that displayed for the postjunctional alpha 1-adrenoceptors in the isolated rabbit aorta. YM-12617 displaced both 3H-WB 4101 and 3H-clonidine binding to rat brain membranes; however, the affinity of YM-12617 for alpha 1-adrenoceptors (pKi = 9.64) was 3800 times higher than that for alpha 2-adrenoceptors (pKi = 6.06). Based on pA2 values obtained in the isolated tissues and pKi values in the binding assays, YM-12617 was 2-18, 36-117 and 1,740-5,750 times more potent than prazosin, phentolamine and yohimbine in antagonizing alpha 1-adrenoceptors, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)