Angiotensin II recognizes two receptor subtypes, AT, and AT2, both of them having been recently cloned. Although AT2 receptors represent 5-10% of angiotensin II receptors in the kidneys of adult rats, their function remains unknown. In the present work, we examined the possible contribution of AT2 receptors to the regulation of pressurenatriuresis in anesthetized rats infused either with the specific AT2 antagonist PD 123319, or with CGP 42112B, an AT2 ligand with agonistic properties. The effects of PD 123319 were examined in a preparation with stable levels of angiotensin II, and in which AT1 receptors were blocked by the specific antagonist losartan. The effects of CGP 42112B were studied in rats deprived of endogenous angiotensin II. AT2 receptor blockade with PD 123319 did not change the renal blood flow while it increased the diuresis and natriuresis. These effects persisted even after full AT1 receptor blockade with losartan. CGP 42112B did not modify the renal blood flow, but dose-dependently decreased urine flow and natriuresis. These results show that, contrary to AT1 receptors, renal AT2 receptors have no effect on total renal blood flow, but blunt the pressure-natriuresis, thus demonstrating that this receptor subtype is involved in a function of importance for body fluid and blood pressure regulation. (J. Clin. Invest. 1995. 95:1394-1397

The influence of renal perfusion pressure (RPP) on renal functions was studied in anesthetized 8-wk-old Lyon hypertensive (LH) and normotensive (LN) rats before and after a specific blockade of prostaglandin (PG) H2-thromboxane (Tx) A2 receptors using GR-32191B. The nervous and hormonal influences on the kidneys were controlled by renal denervation, adrenalectomy, and an infusion of norepinephrine, aldosterone, hydrocortisone, and vasopressin. With the use of inflatable cuffs, RPP was varied from 100 to 125 and then to 150 mmHg. In control conditions, the renal blood flow (RBF) and glomerular filtration rate (GFR) were independent of RPP in both strains. LH kidneys differed from LN controls by an increased preglomerular vasoconstriction as indicated by a similar decrease in RBF and GFR. Moreover, the pressure-natriuresis curve was blunted in LH compared with LN kidneys. GR-32191B did not affect the renal function of LN rats. In LH kidneys, it normalized RBF and renal vascular resistance and improved GFR, whereas it had no effect on the pressure-natriuretic relationship. It is concluded that the elevated preglomerular vascular resistance that characterizes LH rats is dependent on an overstimulation of PGH2-TxA2 receptors whereas these latter are not involved in the control of pressure-natriuresis.

The pressure-natriuresis function in LH rat shows early impairment and aggravates with age. This alteration is observed with, as well as without, controlling the influence of the main extra-renal factors that affect natriuresis.

Vascular aging is characterized by increase in arterial stiffness and remodeling of the arterial wall with a loss of elastic properties. Silicon is an essential trace element highly present in arteries. It is involved in the constitution and stabilization of elastin fibers. The nutritional supply and bioavailability of silicon are often inadequate. Spirulina (Sp), micro algae have recognized nutritional properties and are able to incorporate minerals in a bioavailable form. We evaluated the effects of nutritional supplementation with silicon-enriched spirulina (SpSi) on arterial system structure and function in hypertension. Experiments were performed on hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats supplemented with SpSi or Sp over a period of three months. Arterial pressure, vascular function and morphometric parameters of thoracic aorta were analyzed. SpSi supplementation lowered arterial pressure in SHR and minimized morphometric alterations induced by hypertension. Aortic wall thickness and elastic fibers fragmentation were partially reversed. Collagen and elastin levels were increased in association with extracellular matrix degradation decrease. Vascular reactivity was improved with better contractile and vasorelaxant responses to various agonists. No changes were observed in SHR supplemented with Sp. The beneficial effects of SpSi supplementation evidenced here, may be attributable to Si enrichment and offer interesting opportunities to prevent cardiovascular risks.

The blood pressure reduction produced by an early ACE inhibition in LH rats persists long after treatment withdrawal and is associated with an improvement in renal function. The combination of low doses of perindopril and losartan reveals a long-term effect similar to that of a monotherapy with a higher dose of perindopril.