Altered microvascular response to adenosine in the spontaneously hypertensive rat

Adenosine is a well-known locally active vasodilator metabolite. A major role in blood flow regulation has been ascribed to adenosine. This investigation compared the dose-response curves to adenosine in the cremaster of spontaneously hypertensive rats (SHRs) with Wistar-Kyoto rats (WKYs) at an age when cardiac output and blood flow of the SHR have been shown to be increased (6 weeks). Each concentration (10(-5), 10(-4), and 10(-3) M) was injected retrograde through the femoral artery as a bolus of 100 microliters/sec and 300 microliters/3 sec. Changes in arteriolar diameter were recorded for 3 min. Continuous monitoring techniques enabled detection of differences between strains using an average of the 3-min response (DAVG) and the 3-min response pattern. In contrast, no interstrain differences were observed using the peak diameter response (DMAX). SHRs exhibited a reduced sensitivity to adenosine which was apparent in the dose-response curves based on DAVG with 3-sec injections (P less than 0.02). There was no difference with 1-sec injections. Analysis of the 3-min response pattern showed that SHRs also returned to control diameters faster than WKYs, except at the highest dose when vessels of both strains remained dilated. These results are consistent with the role of metabolic (vasodilator) autoregulation in hypertension. If extracellular adenosine is washed out in the SHR, intraarterial injections of the same concentration of adenosine would cause a reduced response in SHRs.