EFFECT OF ANTIHYPERTENSIVE THERAPY ON A VASCULAR CHANGE IN GENETICALLY HYPERTENSIVE RATS

Isolated tail arteries from stroke-prone spontaneously hypertensive rats (SHRSP), but not normotensive Wistar-Kyoto (WKY) rats, exhibit oscillatory contractions in response to norepinephrine. To establish whether this vascular abnormality is secondary to elevated arterial pressure, SHRSP and WKY were treated with hydralazine and hydrochlorothiazide from weaning to 4 months of age. Hydralazine and hydrochlorothiazide treatment significantly attenuated hypertension development in SHRSP (systolic blood pressure: control SHRSP = 219 .+-. 9 mmHg; treated SHRSP = 143 .+-. 5 mmHg at 15 weeks of age). Helically-cut tail artery strips from all rats were mounted in tissue baths for isometric force recording and exposed to norepinephrine (6 .times. 10-10 - 6 .times. 10-6 M) for 20 min at each concentration. Oscillatory activity was defined as the sum of the magnitudes of all phasic contractions occurring during the final 10 min of NE incubation. There was no significant difference in the magnitude of oscillatory activity between hydralazine/hydrochlorothiazide-treated SHRSP and control SHRSP. From these results we conclude that norepinephrine-induced oscillatory activity in SHRSP is a primary vascular abnormality that is not secondary to high blood pressure.