Renin-angiotensin and development of collateral circulation after renal ischemia

Abstract

Aortic ligation between the origins of the renal arteries in the rat produces a left renal ischemia, renin-dependent hypertension, and a transitory hindlimb paralysis of less than 2 h. Removal of the left ischemic kidney at the time of aortic ligation curtails the rise of blood pressure, plasma renin activity is normal, and paralysis is still present 24 h after surgery. Administration of an angiotensin-converting enzyme inhibitor or saralasin also prevents recuperation from paralysis after aortic ligation. Independent manipulation of the mean arterial pressure or plasma renin activity by pretreatment with reserpine or deoxycorticosterone before surgery shows that the presence or absence of paralysis is dependent on the plasma renin activity and not on the high blood pressure. Blood flow measurements show that paralysis is due to a persistent impairment of blood supply to the hindlimb muscle and not to ischemia of the spinal cord. Infusion of angiotensin II to aortic-ligated, left-renoprival animals tends to restore blood flow to muscle. It is concluded that after renal ischemia the renin-angiotensin system, independent of its hypertensive effect, restores blood flow by stimulating the development of collateral circulation.

Possible pathophysiologic mechanisms supporting the superior stroke protection of angiotensin receptor blockers compared to angiotensin-converting enzyme inhibitors: clinical and experimental evidence

“…Several clinical and experimental studies presented earlier have provided evidence that AII can be cerebroprotective and its effects on ischaemic stroke are mediated through local stimulation of the AT 2 receptors. [36][37][38][39][40] 28,30,33 and especially in elderly patients with isolated systolic hypertension. 29,31 Other mechanisms by which ARBs could reduce the incidence of new or recurrent stroke include the beneficial effects of some ARBs on blood glucose control by increasing insulin sensitivity, 49,50 their platelet antiaggregating effects, [51][52][53][54] their hypouricemic effects 66,67 and their atrial antifibrillatory effects.…”

“…[36][37][38] Fernandez et al 36 showed that AII exerted a protective role against acute vascular ischaemia and transitory paralysis of the hind limbs of the rat by applying an aortic ligature between the kidneys, thus rendering the left kidney ischaemic and producing renovascular hypertension. Removal of the ischaemic kidney reduced the level of plasma rennin activity and blood pressure to within normal values, but the limb's ischaemia persisted for 24 h. Exogenous administration of AII increased the blood pressure and restored the limb ischaemia by increasing the blood flow to the muscles of the hind limb.…”

Angiotensin II Induces Angiogenesis in the Hypoxic Adult Mouse Heart In Vitro Through an AT 2 –B2 Receptor Pathway

“…14 Briefly, 0.5-to 1-mm 3 cubes from the left ventricular myocardium of the mouse heart were placed onto fibrin gels (Sigma-Aldrich) with 500 L of DMEM plus 5% FCS (Biochrom). Heart explants were incubated under normoxia (21% O 2 ) or hypoxia (1% O 2 ) for 7 days.…”

“…2 In mice, activation of pre-existing collateral vascularization that restores blood flow to the acutely ischemic heart was shown to be induced by angiotensin II (Ang II), 3 a key regulator of blood pressure and the main effector of the reninangiotensin-aldosterone system. 4 During ischemia or cancer, Ang II was shown to induce angiogenesis.…”

Captopril reduces aortic and microvascular growth in hypertensive and normotensive rats.

“…After renal ischemia, neither renin nor Ang I, but Ang II, independent of its hypertensive effect, partially restored blood flow to tissues below an aortic ligature by stimulating the development of a collateral circulation. 7 Furthermore, implantation of Ang II in the avascular rabbit cornea not only facilitated the activation of preexisting collateral vascular pathways, but it also had angiogenic properties and therefore could play an active role in the 3A.4A and 5A's fast as well as the slow phases of the development of collateral circulation. 8 In conclusion, the results of these experiments indicate that captopril treatment resulted in a reduction in cross-sectional wall area of aortas and arterioles in normotensive and hypertensive rats, as well as a reduction in the number of small arterioles.…”