Although blood flow to the renal cortex is high and oxygen extraction is low, the renal cortex is remarkably susceptible to hypoxia. Because erythropoietin production has been localized mainly to the renal cortex, the aim of this study was to find a common denominator for both the high susceptibility to hypoxia and oxygen sensing within the renal cortex. By direct measurement of oxygen pressure with microcoaxial needle sensors at superficial glomeruli of the in situ kidney of anesthetized Munich-Wistar-Frömter rats, we obtained mean partial pressure of O2 (PO2) values of 46 +/- 13 (SD) mmHg (n = 71). The simultaneously measured systemic PO2 in arterial blood was 90 +/- 8 mmHg (n = 54). Changing the respirator gas from air to pure oxygen enhanced systemic arterial PO2 to 593 +/- 27 mmHg, whereas PO2 at the superficial glomeruli increased only to a mean of 80 +/- 28 mmHg (n = 71). These data suggest significant preglomerular shunting of oxygen within the cortical vasculature, most likely between interlobular vessels, which are arranged in a countercurrent fashion and represent quantitatively the largest contact area between arteries and veins within the renal cortex.
Rat calcitonin gene-related peptide (CGRP alpha; EC50, 1 nM) was shown to stimulate cAMP formation in cultured rat renal mesangial cells. CGRP concentration dependently (EC50, 1 nM) also inhibited contraction of mesangial cells by angiotensin II (10 nM). Angiotensin II (10 nM) caused a transient increase of the intracellular calcium concentration from 140 nM to 480 nM in the mesangial cells, but these calcium transients were not altered by CGRP. CGRP (10 nM) decreased vascular resistance in the isolated rat kidney perfused at constant pressure (100 mm Hg; P less than 0.01). The decreased vascular resistance was accompanied by a rise of the glomerular filtration fraction. CGRP, moreover, attenuated the effects of angiotensin II on renal vascular resistance and glomerular filtration (P less than 0.01). In conclusion, CGRP causes relaxation of renal mesangial cells and decreases renal vascular resistance. As a result CGRP raises glomerular filtration and the filtration fraction. The effect may be linked to cyclic AMP formation. Thus, regulation of renal vascular and glomerular function may represent a novel action of CGRP apart from its cardiovascular effects.
Cross circulation was performed in 54 couples of spontaneously hypertensive and normotensive rats. Blood was pumped through two anastomoses between the carotid arteries and external jugular veins in both directions with equal flow rate. In normotensive rats cross-circulated with untreated spontaneously hypertensive rats mean arterial pressure increased by 20.9±12.2 mm Hg (p<0.01). Administration of digoxin antibody in a dose binding 0.25 mg digoxin to the spontaneously hypertensive rats before cross circulation prevented the transmission of hypertension to the normotensive rat, whereas chemical sympathectomy with 6-hydroxydopamine and intravenous injection of inactive Fab fragments had no inhibitory effect. It is concluded that, in this strain of spontaneously hypertensive rats, a circulating hypertensive factor exists. The factor binds to digoxin antibody and is not produced in sympathetic nervous tissue. (Hypertension 1989;14:61-65) T here are several indications for the role of a circulating vasopressor agent in primary hypertension. First, hypertensive plasma enhances the vasoconstrictor effect of noradrenaline and angiotensin II. -2 Second, parabiosis experiments with spontaneously hypertensive rats demonstrated the transmission of hypertension.3 -5 Third, injection of hypertensive plasma or other blood components increased blood pressure in normotensive rats.6 -8 Likewise, a transmission of hypertension from spontaneously hypertensive to normotensive rats has been demonstrated by cross circulation. 9Early experiments with parabiosis 10 ' 11 and recent cross circulation studies pointed to an important role of kidneys and adrenal glands for the production of the hypertensive factor. Injection of plasma from nephrectomized hypertensive rats failed to increase blood pressure in normotensive rats. 6 The transmission of hypertension by cross circulation can be prevented by nephrectomy and adrenalectomy in the spontaneously hypertensive rat. 9Although the production of the hypertensive factor in the spontaneously hypertensive rat was localized by several studies in the kidneys or adrenal glands, the structure of the hypertensive factor is yet unknown. Therefore, in the present study, cross circulation was used as a bioassay of the circulating hypertensive factor.From the Medical University, Poliklinik, Albert-Schweitzer, MOnster, FRG.Address for correspondence: Dr. Walter Zidek, AlbertSchweitzer-Str. 33, D-4400, Mflnster, FRG.Received March 10, 1987; accepted January 19, 1989. As to the nature of the yet unidentified agent, several lines of evidence point to a circulating sodium-potassium adenosine triphosphatase (Na,K-ATPase) inhibitor. First, in essential hypertensive individuals the ability of plasma to inhibit Na,K-ATPase has been repeatedly demonstrated. Recently, neuropeptide Y has been described as a vasopressor and natriuretic agent 23 -24 and may thus fulfill the criteria for the hypothetical natriuretic hormone. Neuropeptide Y has been shown to be produced in sympathetic nerve cells, 25 and its sy...
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