RELATIONSHIP BETWEEN NIFEDIPINE SENSITIVITY OF AORTAE AND BLOOD-PRESSURE OF STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

1. We have previously described an increased sensitivity to inhibition by nifedipine of noradrenaline-induced contractures of blood vessels in hypertension. In this study we have investigated whether changes in blood pressure (BP) change the sensitivity to nifedipine and K+ of ao rtic rings from normotensive (Wistar-Kyoto rats, WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP were treated with: hydralazine plus hydrochlorothiazide; captopril plus hydrochlorothiazi de; hydralazine plus guanethidine; or captopril alone, WKY rats were t reated with deoxycorticosterone acetate (DOCA) and NaCl. Treatment com menced from 5 weeks of age and continued until 13-15 weeks. 3. The SHR SP treatments produced similar reductions in BP, and the BP of all the treated groups were significantly lower than the mean BP of untreated SHRSP (201.0 +/- 7.7 mmHg). The mean BP of the treated WKY rats (134. 2 +/- 7.6 mmHg) was significantly higher than the mean BP of the untre ated WKY rats (86.8 +/- 7.4 mmHg). 4. An area-under-curve (AUG) analys is of the inhibitory effects of nifedipine on responses of aortae to n oradrenaline showed no differences between treated and untreated SHRSP groups (overall mean 40.6 +/- 1.9% and 43.4 +/- 3.4% inhibition of co ntrol AUC, respectively), or between DOCA-salt treated WKY and untreat ed WKY groups (58.8 +/- 5.9 and 64.8 +/- 2.3, respectively). Noradrena line-induced contractures of aortae from all SHRSP groups were signifi cantly more sensitive to inhibition by nifedipine than aortae from bot h WKY groups. 5. The molar concentration of agonist required to evoke 50% of the maximum response (EC(50)) values for potassium chloride (KC I) were significantly increased in the aortae of all treated SHRSP gro ups in comparison to those from untreated SHRSP (treated SHRSP groups, 15.53 +/- 0.68 mmol/L vs untreated SHRSP group, 11.3 +/- 1.10 mmol/L) . The EC(50) values for KCl for the aortae from the DOCA-treated WKY r ats were significantly less than those from aortae of the untreated WK Y (11.80 +/- 0.80 and 17.08 +/- 1,50 mmol/L, respectively).