ARTERIAL CONTRACTIONS INDUCED BY CUMULATIVE ADDITION OF CALCIUM IN HYPERTENSIVE AND NORMOTENSIVE RATS - INFLUENCE OF ENDOTHELIUM

Responses to cumulative addition of Ca2+ (0.2-2.5 mM) after precontrac tion with potassium chloride (KCl) and noradrenaline in Ca2+-free medi um were studied in isolated mesenteric arterial rings from spontaneous ly hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The Ca2+ contr actions in 125 mM KCl-stimulated endothelium-denuded rings in the pres ence of atenolol (10 mu M) and phentolamine (10 mu M) were less marked in SHR than WKY, although the contractions to high concentrations of KCI in normal organ bath Ca2+ (1.6 mM) were similar in these strains. The difference in Ca2+ contractions between SHR and WKY during KCl sti mulation was also present after 10-min pretreatment with 1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) i n Ca2+-free medium. However, when noradrenaline (1 mu M) was used as t he agonist the Ca2+ contractions of endothelium-denuded rings in the t wo strains were comparable, while exposure to EGTA reduced these respo nses more effectively in SHR than WKY. Nifedipine (0.5 nM and 10 nM in KCl- and noradrenaline-stimulated rings, respectively) more efficient ly inhibited the Ca2+ contractions in hypertensive than in normotensiv e rats. The presence of intact vascular endothelium attenuated the con tractions to Ca2+ addition comparably (during KCl stimulation) or even more (during noradrenaline) in SHR when compared with WKY. N-G-nitro- L-arginine methyl ester (L-NAME, 0.1 mM) counteracted this attenuation correspondingly in WKY and SHR, and L arginine (1 mM) restored it in both strains, whereas indomethacin (10 mM) was without effect on the r esponse. However, mesenteric arterial relaxations induced by the endot helium-dependent agonists acetylcholine and ADP in noradrenaline-preco ntracted (1 mu M) rings were clearly impaired in SHR, and also L-NAME (0.1 mM) reduced the responses to acetylcholine more efficiently in SH R. In contrast, the relaxations to acetylcholine and ADP in KCl-precon tracted (60 mM) rings in the absence and presence of L-NAME were compa rable between the two strains. In conclusion, attenuated contractile r esponse to cumulative Ca2+ addition during stimulation with KCl clearl y differentiated arterial smooth muscle of hypertensive and normotensi ve rats, suggesting altered function of cell membrane in SHR. The more pronounced effect of nifedipine on the response indicates abnormal fu nction of voltage-dependent Ca2+ channels, and higher diminishing effe ct of EGTA on the contraction during noradrenaline suggests exaggerate d action of the chelator on membrane-bound Ca2+ in SHR. Interestingly, the depressant effect of intact endothelium on the Ca2+ con traction response, mediated largely via nitric oxide, was not attenuated in SHR . Furthermore, impaired endothelium-dependent agonist-induced relaxati ons can be attributed to reduced release of endothelium-derived hyperp olarizing factor in this type of genetic hypertension.