INFLUENCE OF GRADED CHANGES IN VASOMOTOR TONE ON THE CAROTID ARTERIALMECHANICS IN LIVE SPONTANEOUSLY HYPERTENSIVE RATS

1 The contribution of vasomotor tone to the increased stiffness of car otid arteries in living spontaneously hypertensive rats (SHR) is large ly unknown. Whether a reduced vascular tone is associated with an incr ease or a decrease in arterial stiffness in vivo remains to be determi ned. The goal of the present investigation was to show that a decrease in vascular tone is associated with a decrease in arterial stiffness, independent of the structural composition of the arterial wall. 2 New high resolution echo-tracking techniques were used to evaluate pulsat ile changes of carotid blood pressure and diameter following transient and graded changes of vasomotor tone produced by the dihydropyridine derivative, isradipine. Treatment for 8 weeks was given to groups of S HR rats either with a low (0.6 kg day(-1)) or a high (2.6 mg kg(-1) da y(-1)) dose. Another SHR group received an acute dose of 2.6 mg kg(-1) day(-1). Results were compared to those of placebo-treated Wystar-Kyo to (WKY) and SHR rats. Whatever the dosage, acute or chronic calcium b lockade caused a decrease in blood pressure which was maximal 1 h afte r administration and disappeared after the 16th h. Carotid arterial th ickness and the composition of the arterial wall was determined from h istomorphometry. 3 In placebo-treated SHR, the inverse relationship re lating blood pressure to carotid arterial distensibility was significa ntly shifted toward higher values of blood pressure compared to the cu rve of normotensive placebo-treated WKY rats. The curve of SHR receivi ng chronically a non antihypertensive (0.6 mg kg(-1) day(-1)) isradipi ne dose prolonged that of placebo-treated SHR toward lower values of b lood pressure, so that carotid distensibility was significantly higher than in WKY for the same diameter and blood pressure level (145 mmHg) . With administration of a chronic antihypertensive dose (2.6 mg kg(-1 ) day(-1)) causing a significant decrease in arterial thickness, the c urve of SHR was transiently shifted towards the WKY curve, resulting i n a normal arterial function. Acute antihypertensive calcium blockade with a single isradipine dose (2.6 mg kg(-1) day(-1)) caused a similar shift in the pressure-distensibility curve toward the WKY curve altho ugh the histomorphometric composition of the arterial wall differed si gnificantly from that of chronically treated animals. 4 The study prov ides evidence that, in living SHR submitted to calcium blockade, (i) a low dose of isradipine causing no substantial antihypertensive effect is associated with a significant elevation of carotid arterial disten sibility for the same pressure and diameter as normotensive controls, and (ii) an acute or chronic dose causing a substantial antihypertensi ve effect is associated with a transient shift of the SHR distensibili ty-pressure curve toward a physiological arterial function, increasing carotid distensibility for the same pressure and diameter as WKY cont rols. Since such findings were observed independently of the histomorp hometric composition of the arterial wall, they imply that the transie nt decrease in arterial stiffness produced by calcium blockade should involve specific changes in the connections between arterial smooth mu scle and extracellular matrix.