Shannon R P, Gelpi R J, Hittinger L, Vatner D E, Homcy C J, Graham R M, Vatner S F
Department of Medicine, Harvard Medical School, Boston, MA.
Circ Res. 1991 Feb;68(2):543-54. doi: 10.1161/01.res.68.2.543.
We studied the inotropic responses to intravenous infusions of norepinephrine in nine conscious chronically instrumented dogs before and early (2-4 weeks) in the development of perinephritic hypertension; seven conscious dogs were studied later (approximately 14 weeks), during a more stable phase of hypertension. perinephritic hypertension was associated with a 24% increase in left ventricular (LV) mass during developing hypertension; no further increase was seen during the stable hypertension phase. LV end-systolic stress was increased early (p less than 0.01) but was normalized later. The LV end-systolic stress-volume relation demonstrated an enhanced contractile response to norepinephrine during developing hypertension, which returned toward control later in the course of stable hypertension. The LV dP/dt responses to norepinephrine (0.4 microgram/kg/min) were significantly greater during developing hypertension (7,509 +/- 337 mm Hg/sec, p less than 0.05) compared with the control period (4,737 +/- 286 mm Hg/sec) and returned toward the control value during stable hypertension (5,168 +/- 465 mm Hg/sec). The enhanced inotropic responses to norepinephrine in developing hypertension were preserved in the presence of ganglionic blockade, suggesting that the augmentation was not mediated via reflex mechanisms. These physiological responses were associated with an increase in beta-adrenergic receptor density, but no significant change in basal or maximal adenylate cyclase stimulation occurred during developing hypertension. Thus, in contrast to prior studies in anesthetized animals, the inotropic response to beta-adrenergic stimulation is not depressed in conscious dogs but is enhanced selectively during the development of hypertension and maintained during stable hypertension.
我们研究了9只清醒的、长期植入仪器的犬在肾周炎高血压发生前及早期（2 - 4周）静脉输注去甲肾上腺素时的变力反应；7只清醒犬在高血压更稳定阶段（约14周）进行了研究。肾周炎高血压在高血压发展过程中与左心室（LV）质量增加24%相关；在稳定高血压阶段未观察到进一步增加。LV收缩末期应力在早期增加（p < 0.01），但后来恢复正常。LV收缩末期应力 - 容积关系显示，在高血压发展过程中对去甲肾上腺素的收缩反应增强，在稳定高血压后期恢复至对照水平。与对照期（4,737 ± 286 mmHg/秒）相比，在高血压发展过程中，LV对去甲肾上腺素（0.4微克/千克/分钟）的dP/dt反应显著更大（7,509 ± 337 mmHg/秒，p < 0.05），并在稳定高血压期间恢复至对照值（5,168 ± 465 mmHg/秒）。在存在神经节阻断的情况下，高血压发展过程中对去甲肾上腺素增强的变力反应得以保留，表明这种增强不是通过反射机制介导的。这些生理反应与β - 肾上腺素能受体密度增加有关，但在高血压发展过程中基础或最大腺苷酸环化酶刺激未发生显著变化。因此，与先前对麻醉动物的研究相反，清醒犬对β - 肾上腺素能刺激的变力反应未受抑制，而是在高血压发展过程中选择性增强，并在稳定高血压期间维持。
