Inotropic response to norepinephrine is augmented early and maintained late in conscious dogs with perinephritic hypertension.
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.
Shannon
R P
RP
Department of Medicine, Harvard Medical School, Boston, MA.
Gelpi
R J
RJ
Hittinger
L
L
Vatner
D E
DE
Homcy
C J
CJ
Graham
R M
RM
Vatner
S F
SF
D000818:Animals; D004285:Dogs; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D009638:Norepinephrine / Q000494:pharmacology*; D010501:Perinephritis / Q000150:complications / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
D005730:Ganglionic Blockers; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D009638:Norepinephrine