Development of hypertension from unilateral renal artery stenosis in conscious dogs.

Abstract

The renal and systemic changes after stenosis of the left renal artery (n=S) or sham stenosis (n=6) in conscious dogs were studied sequentially over 25 days. Stenosis produced a prompt rise in arterial pressure, which was at all times due to reduced peripheral vascular conductance, with no increase in cardiac output despite initial evidence of mild fluid retention. The decrease in peripheral conductance was attributable to 1) the stenotic kidney (25% of the total and due to the mechanical effect of the stenosis itself), 2) the nonstenotic kidney (about 15% of the total and not caused by angiotensin II), and 3) the nonrenal vasculature (60%). The decrease in conductance in the nonrenal vasculature was due partly to angiotensin II, but there was also a gradually developing non-angiotensin II component Acute administration of captopril caused significantly greater changes in arterial pressure and peripheral conductance throughout the period of stenosis than before stenosis (and greater than in sham-stenosis dogs), indicating that angiotensin II was constricting the peripheral vasculature even when plasma renin levels were no longer elevated. In the stenotic kidneys, captopril produced a fall in renal vascular resistance, but renal blood flow did not rise because there was an approximately equal rise in the resistance of the stenosis. There was no evidence for a role for the autonomic nervous system in the hypertension, as ganglion blockade (pentolinium) had similar hemodynamic effects before and after stenosis. Thus, the hypertension was due at all times to reduced peripheral conductance, with the two kidneys responsible for 40% of this reduced conductance. (Hypertension 1990;16:441-451) U nilateral renal artery stenosis produces hypertension in humans and in experimental animals, including rats (see Reference 1), sheep, 2 and dogs, 3 " 5 provided that the stenosis is severe enough. 4 Evidence from previous experiments suggests that both the renin-angiotensin system and the autonomic nervous system are involved in the development of this two-kidney, one clip (2K 1C) form of hypertension. 8 However, gaining a complete understanding of the early stages of the hypertension has been complicated by the fact that stenosis has, with very few exceptions, been induced during surgery in anesthetized animals. Surgery itself disturbs the renin-angiotensin system, autonomic reflexes, and body fluid homeostasis, 9 the very factors thought to be involved in the initiation and development of hypertension.We recently published a comprehensive analysis of the hemodynamic events involved in the first hour of Received October 11, 1989; accepted in revised form May 25, 1990. this form of renal hypertension in conscious dogs. 10This showed that the initial rise in arterial pressure was due entirely to decreased peripheral vascular conductance (increased resistance) and, remarkably, that the kidneys themselves were responsible for almost half of this fall in conductance. In the case of the stenotic kidney, its conductance was reduced...

Total peripheral resistance responsiveness during the development of secondary renal hypertension in dogs

“…The present study extends previous work by our group in this model [10][11][12][13][14][15][16]. The haemodynamic responses to stenosis were studied under normal (closed-loop) conditions and in the open-loop situation (i.e.…”

Development of Hypertension and Effects of Benazepril Hydrochloride in a Canine Remnant Kidney Model of Chronic Renal Failure

“…renovascular hypertension, or secondarily to loss of functioning nephrons. Occurrence of renovascular hypertension in dogs has been verified by the Goldblatt model in which hypertension is induced by constricting the renal arteries [3,4,19,23,32]. However, in order to consider renal hypertension in small animal practice, more common nephron loss-associated hypertension is important.…”

“…Causes of secondary hypertension include renoparenchymal diseases, renovascular diseases, diabetes, Cushing syndrome, primary hyperaldosteronism, pheochromocytoma and hypothyroidism and, of those, renoparenchymal disease-associated hypertension is most common in humans [24]. The mechanism of renal hypertension is thought to involve renal insufficiency-associated body fluid retention, increases in cardiac output and peripheral vessel resistance, activation of the renin-angiotensin-aldosterone (RAA) system and suppression of the kallikrein-kinin-prostaglandin system [2,3,17].A link between chronic renal failure and hypertension has been suggested in dogs and cats [1,6,12,13,22,26,27,29,30,34,[36][37][38]. Activation of the RAA system and development of hypertension in association with renal failure have been reported in cats [20,30,41].…”

Marine oils dose-dependently inhibit vasoconstriction of forearm resistance vessels in humans.

“…The brachial artery was cannulated (3.0F, 5-cm catheter; Cook, Australia) for intra-arterial pressure recordings as well as for local, sequential infusions of norepinephrine (25,50, and 100 ng/min) and angiotensin II (8,16, and 32 ng/min). Each concentration was infused at 4 ml/min over 2 minutes.…”