Courtney K R, Colwell W T, Jensen R A
Prostaglandins. 1978 Sep;16(3):451-9. doi: 10.1016/0090-6980(78)90224-1.
Prostaglandins PGE2, PGE1, PGF2alpha, and PGE1 substantially increase automaticity in SA-nodal, right atrial preparations excised from guinea pigs. This natural pacemaker tissue is sensitive to nanomolar doses of PG with, for example, 10(-8) M PGE2, increasing SA rate by about 20%. If these preparations are pretreated with 2 micrometer indomethacin, a blocker of endogenous prostaglandin synthesis, then spontaneous rate drops and subsequent rate increases due to PGE2 administration can be more easily demonstrated. Guinea pig pacemaker tissue differs from similar rabbit tissue not only in that it is directly responsive to PGE2, but also in that PGE2 does not depress the absolute response to transmural stimulation (adrenergically mediated rate increase). The positive chronotropic responses to PGE2 also occur when the guinea pig tissue is pretreated in 0.6 micrometer propranolol, which causes blockade of beta-adrenergic receptors. The pacemaker myocardium in the guinea pigs thus appears to be directly stimulated by exogenous PGE2 at very low doses. The observation that 2 micrometer indomethacin reduces SA-nodal rate suggests the presence of a very sensitive, functionally important, PGE-like system which modulates heart rate in this mammalian species.
前列腺素PGE2、PGE1、PGF2α和PGE1能显著提高从豚鼠身上切除的窦房结、右心房标本的自律性。这种天然起搏组织对纳摩尔剂量的前列腺素敏感,例如,10^(-8)M的PGE2可使窦房结速率提高约20%。如果用2微摩尔的吲哚美辛(一种内源性前列腺素合成阻滞剂)对这些标本进行预处理,那么自发速率会下降,随后由于给予PGE2而导致的速率增加就更容易显现出来。豚鼠起搏组织与类似的兔组织不同,不仅在于它对PGE2有直接反应,还在于PGE2不会抑制对跨壁刺激(肾上腺素能介导的速率增加)的绝对反应。当豚鼠组织用0.6微摩尔的普萘洛尔预处理(这会导致β-肾上腺素能受体阻滞)时,对PGE2的正性变时反应也会出现。因此,豚鼠的起搏心肌似乎在非常低的剂量下就受到外源性PGE2的直接刺激。2微摩尔的吲哚美辛降低窦房结速率这一观察结果表明,存在一个非常敏感、功能上很重要的、类似PGE的系统,该系统在这种哺乳动物中调节心率。