Vascular reactivity to ATP in vitro in experimental hypertension

MICROVASCULAR

RESEARCH

4,298-299 (1972)

BRIEF Vascular

COMMUNICATION

Reactivity

to ATP in Vitro in Experimental Hypertension G. S. HARRIS

Department of Medicine, University of Melbourne, Austin Hospita!, Heidelberg 3084, Victoria, Australia Received November 23,1971

In experimental hypertension there is an increasedarterial reactivity to pressoragents. Since no significant increase in sympathetic nerve activity can be demonstrated in hypertensive animals, it is probable that the increased vascular reactivity observed in hypertension is due to an increased reactivity of the arterial smooth muscle cell. Studies on the arteries in hypertension have shown an increased activity of the enzymes AMPase, ADPase, and ATPase. ATPase activity is known to be associated with Na+, K+ transport and to be associatedwith the level of membrane calcium which is reported to be increased in arteries from hypertensive animals. Since ATP intraluminally in vitro constricts a buffer-perfused arterial bed in the rat hind quarter, the IOO-

Renal Hypertensive I

(n = 23)

T/ 1

0

,I

I

.33 .67

1.25

ATP

dose

, 2.50

3.75

mg

FIG. 1. Dose-response relationship of increase ATP concentration. Copyright 0 I972 by Academic Press, Inc. All rights of reproduction in any form reserved.

in constrictor

298

response

in millimetres

of mercury

to

BRIEF

COMMUNICATION

299

reactivity of this arterial bed to single dosesat ATP was examined by obtaining doseresponsecurves in hypertensive and control rats. Wistar rats were subjected to right nephrectomy and left renal artery clipping. Twelve weekslater the blood pressure was measured with the animals unanaesthetized using a pneumatic pulse transducer applied to the tail. A blood pressureof greater than 150 mm Hg was considered to indicate hypertension and one of less than 130 mm Hg was considered normal. After the blood pressurehad beenmeasured,all rats were killed by a blow on the head, the lower abdominal aorta wascannulated, and the hind quarters perfused with McEwan’s solution at 37” equilibrated with 95 % O2and 5 p/, COZ. The perfusion rate was varied so as to give a perfusion pressure of 60 mm Hg. A doseresponsecurve to ATP was then obtained within 20 min of the start of perfusion. The dose-responsecurves of rat hind quarters to ATP show that hypertensive rats have an increased response to ATP when compared to renal-clipped normotensive rats (Fig. I). The reactivity of the hind quarters of hypertensive rats to ATP at the highest dose of ATP used was 110% greater than the clipped normotensive rats (2 p < 0.0025). This increased reactivity to ATP is in the same direction as the histochemically observed change in ATPase activity in the arteries of hypertensive animals. It is, therefore, a demonstration of change in enzyme activity in the arteries of hypertensive animals which is associatedwith a similar changein arterial reactivity to the appropriate agonist. Since several ATPase systems exist, it would seem important to know which of the systemsare affected during the development of hypertension.