A variety of experimental hypertensions in rats has been available for the evaluation of the anti-hypertensive agents as well as for the mechanism studies of essential hyperten sion. The spontaneously hypertensive (SH) rat with 100 per cent incidence of heredity has been separated from the Wistar rats (1). Though the hypertension develops in the early stage without certain etiology, the animals in the advanced stage exhibit the vascular lesions such as periarteritis nodosa, nephrosclerosis and cardiac lesions (2-5). Recently, Okamoto et al. (6,7) and Matsumoto (8) have indicated further some involvement of neural factors in development and maintenance of the hypertension.In order to elucidate pharmacologically the mode of the hypertension in the SH rats, the depressor responses to the anti-hypertensive agents were observed comparatively be tween in the SH and normotensive (N) rats.
MATERIALS AND METHODSFor the establishment of a dose-response relationship of the anti-hypertensive agents, specific pathogen free SH* (F13,14) and N rats of 17 to 25 weeks of age were used as a group of 5 rats per one dose level of each drug. The daily administrations of the following drugs in the conventional SH and N rats were as follows: 19 female SH rats (F,,,,,) of 6 and 15 weeks of age for hydrochlorothiazide, 8 SH and 8 N rats of 10 and 19 weeks of age for cmethyl DOPA and 18 SH and 18 N rats (7 to 12 months of age) for hydralazine, reserpine and guanethidine. The animals were kept in a room at a temperature of 23 to 24°C and fed stock diet and tap water ad libitum.Systolic blood pressure was determined in unanesthetized animals using Nakao et al.'s tail cuff method (9). Heart rate was calculated from the amplified pulse waves being taken during the blood pressure measurement. The measurements were carried out at one hour before and at 1, 4, 7 or 8, 24 and 48 hours after drug administration. Prior to the administration, the animals in our experiments were accustomed to the measurement handling 2 or 3 times in the preceding week.* Production of specific pathogen free animals were carried out by us in the spontaneously hypertensive and normotensive rats.