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 mechanism of action and possible role of the potent vasodilator bradykinin (BK) in regulation of arteriolar tone were investigated. Changes in diameter of third-order arterioles of cremaster muscle in response to topical 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 B2-receptor antagonist, the presence of kinin receptors in arterioles was studied. In control preparations, 10(-5) M arachidonic acid (AA), 0.5 x 10(-6) M acetylcholine (ACh), and 10(-5) M adenosine (ADO) evoked dilation of arterioles of up to 70% of resting diameter. BK (10(-9), 10(-8), 10(-7), and 10(-6) M) elicited dose-dependent arteriolar dilations (1.3 +/- 1.3, 4.1 +/- 0.5, 10.3 +/- 1.6, and 13.3 +/- 1.3 microns, 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: to 2.9 +/- 1.8 microns). Also, whereas Hoe-140 significantly reduced basal arteriolar diameters (from 16.7 +/- 0.9 to 13.8 +/- 1.1 microns, P < 0.05), it did not affect constrictions to norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)
Koller
A
A
Department of Physiology, New York Medical College, Valhalla 10595, USA.
Rodenburg
J M
JM
Kaley
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply*; D009638:Norepinephrine / Q000494:pharmacology; D017257:Ramipril / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; C052549:ramiprilat; C065679:icatibant; D017257:Ramipril; D001920:Bradykinin; D009638:Norepinephrine