Vascular reactivity during the development of two-kidney, one-clip Goldblatt hypertension in conscious dogs.
This study evaluates the sequential changes in vascular reactivity in conscious dogs during the early and late phases of two-kidney, one-clip Goldblatt hypertension (2-KGH) produced by unilateral renal artery constriction (URAC). The in vivo responses to serotonin (5-HT), norepinephrine (NE), angiotensin II (Ang II), prostacyclin (PGI2), acetylcholine (ACH), and nitroglycerin (GTN) were reproducible and stable throughout the 32-day period of study in dogs subjected to sham URAC. The vascular responses to 5-HT, Ang II, and PGI2 were enhanced day 1 post-URAC, before mean arterial pressure (MAP), cardiac output (CO), or total peripheral resistance (TPR) increased. The magnitude of the enhanced reactivity progressed on days 4 and 32 post-URAC, as hypertension developed. The pressor responses to NE did not change from pre-URAC values until CO and MAP were elevated. The vasodepressor responses to ACH and GTN diminished over a 12-day period post-URAC, in parallel with the change in CO, but prior to any increase in TPR. These data suggest that in dogs with 2-KGH changes in vascular reactivity precede the development of the increased MAP and TPR of hypertension. The lack of uniformity of the onset of the reactivity changes to the different agonists suggests that both intrinsic factors and pressure changes modify the vascular wall in the early and later stages of 2-KGH.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006977:Hypertension, Renal / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D000804:Angiotensin II; D012701:Serotonin; D009638:Norepinephrine