beta-Adrenergic relaxation in mesenteric resistance arteries of spontaneously hypertensive and Wistar-Kyoto rats: the role of precontraction and intracellular Ca2+.
An attenuated beta-adrenergic vasodilation of small arteries may help explain the increased peripheral resistance in hypertension. To investigate this, we compared the isoprenaline-induced relaxation of mesenteric resistance arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using a small vessel myograph. The arteries had similar diameters, but the contractile force induced by cumulative addition of K+ (10-130 mM) was 1.3-fold higher for the SHR. The beta-adrenoceptor-mediated relaxation of arteries, precontracted with 40 mM K+, was significantly less in SHR (41 +/- 3%, n = 11) than in WKY (56 +/- 3%, n = 15, p = 0.003), and the pD2 value for isoprenaline was significantly lower in SHR (7.13 +/- 0.09 vs. 7.41 +/- 0.07, p = 0.02). In contrast, when precontracted with phenylephrine (PE, alpha 1-adrenoceptor agonist, 3-10 microM), isoprenaline relaxation was almost complete in both SHR and WKY, and the pD2 value for isoprenaline did not differ between strains. Forskolin induced complete relaxation of both precontractions. Because the beta-adrenergic relaxation of the mesenteric resistance arteries was attenuated only after K(+)-precontraction, we conclude that alterations in this precontracting mechanism in SHR rather than a defect in the beta-adrenoceptor system may provide an explanation for the decreased relaxation in these vessels. Intracellular Ca2+ measurements and a review of the literature support this conclusion.
Blankesteijn
W M
WM
Department of Medicine, University Hospital Nijmegen, Netherlands.
Raat
N J
NJ
Willems
P H
PH
Thien
T
T
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D010656:Phenylephrine; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium