EFFECTS OF HOE-140 AND RAMIPRILAT ON ARTERIOLAR TONE AND DILATION TO BRADYKININ IN SKELETAL-MUSCLE OF RATS

In skeletal muscle of pentobarbital sodium-anesthetized rats, the mech anism of action and possible role of the potent vasodilator bradykinin (BK) in regulation of arteriolar tone were investigated. Changes in d iameter of third-order arterioles of cremaster muscle in response to t opical administration of BK and other vasoactive agents were measured with an image-shearing monitor and recorded with video microscopy. All agonists were administered topically on the exteriorized muscle. With use of Hoe-140, a B-2-receptor antagonist, the presence of kinin rece ptors in arterioles was studied. In control preparations, 10(-5) M ara chidonic acid (AA), 0.5 x 10(-6) M acetylcholine (ACh), and 10(-5) M a denosine (ADO) evoked dilation of arterioles of up to 70% of resting d iameter. BK (10(-9), 10(-8) 10(-7), and 10(-6) M) elicited dose-depend ent arteriolar dilations (1.3 +/- 1.3, 4.1 +/- 0.5, 10.3 +/- 1.6, and 13.3 +/- 1.3 mu m, respectively). In the presence of 10(-7) M Hoe-140, dilations to AA, ACh, and ADO were not affected, but those to 10(-9)- 10(-7) M BK were eliminated or significantly inhibited (10(-6) M BK: t o 2.9 +/- 1.8 mu m) Also, whereas Hoe-140 significantly reduced basal arteriolar diameters (from 16.7 +/- 0.9 to 13.8 +/- 1.1 mu m, P < 0.05 ), it did not affect constrictions to norepinephrine. Similar experime ntal protocols with 10(-6) M ramiprilat (a kininase II or angiotensin- converting enzyme inhibitor) demonstrated a substantially enhanced dil ation (peak and duration) of arterioles to the various doses of BK and did not affect the responses to norepinephrine, ACh, and ADO. On the other hand, ramiprilat significantly increased basal arteriolar diamet er (from 19.1 +/- 0.6 to 23.3 +/- 0.8 mu m). Changes in basal tone to ramiprilat or Hoe-140 were not different when the PO2 of the suffusion solution was changed from ambient to 35-40 mmHg. Thus our findings su ggest that, in rat skeletal muscle arterioles, BK elicits dilation via B-2 receptors and participates in the regulation of basal arteriolar tone.