No abstract

In a previous study of the changes in glomerular structure in the isolated perfused kidney (IPK), perfusion at high pressures lead to an enlargement of the glomerular tuft and to the formation of giant capillaries. The present paper analyzes the morphological and dimensional changes of the peripheral glomerular capillary wall under these circumstances. The enlargement of glomerular capillaries at high pressure perfusion was accompanied by a considerable increase in the surface area of the glomerular basement membrane (GBM). The podocyte as well as the endothelial layer perfectly adapted to the acute challenge in covering increasing GBM area. The interdigitating foot process pattern showed up in an ideal arrangement. The capillary wall expansion was associated with a significant increase in total pericapillary slit area. Compared to the corresponding low pressure groups (65 mm Hg, without and with the application of vasodilators) the slit area increased in the high pressure groups (105 mm Hg, without and with vasodilator) by approximately 50 and 75%, respectively. This increase of the slit area was mainly due to an increase in slit length; the slit width remained fairly constant. These findings indicate that the pericapillary wall is distensible based on a distensibility of the GBM. We suggest that the contractile apparatus of podocyte foot processes regulates the expansion of the GBM.

No abstract

It has been suggested that tissue-specific expression of the genes of the renin-angiotensin system (RAS) leads to local generation of angiotensin (ANG) II with specific physiological implications. We demonstrate here that an intracellular RAS exists in adrenal glomerulosa cells; 60 h after bilateral nephrectomy and hemodialysis, renin and prorenin were eliminated from the circulation, whereas intra-adrenal renin content increased (control rats: 2 +/- 0.5 ng ANG I.mg-1.h-1; anephric rats: 25 +/- 2). Thus renin is produced locally within adrenal cells. We obtained immunocytochemical and biochemical evidence for the presence of renin within intramitochondrial dense bodies of the zona glomerulosa. After nephrectomy, dense bodies increased in number, size, and renin content (control rats: 2.5 +/- 0.7 ngANGI.mg-1.h-1; anephric rats: 43 +/- 7). Angiotensin-converting enzyme (ACE) was also present within mitochondria and their dense bodies. In addition, in adrenal cortex of anephric rats, giant dense bodies were observed, which contain renin and strongly react with an anti-angiotensinogen antibody. The localization of renin, ACE, and angiotensinogen at these sites provides new evidence for the existence of an intracellular adrenal RAS.

The relationship between renal artery pressure (RAP), renal blood flow (RBF), glomerular filtration rate (GFR) and the renal venous-arterial plasma renin activity difference (PRAD) was studied in 22 chronically instrumented, conscious foxhounds with a daily sodium intake of 6.6 mmol/kg. RAP was reduced in steps and maintained constant for 5 min using an inflatable renal artery cuff and a pressure control system. Between 160 and 81 mm Hg we observed a concomitant autoregulation of GFR and RBF with a high precision. The "break off points" for GRF- and RBF-autoregulation were sharp and were significantly different from each other (GFR: 80.5 +/- 3.5 mm Hg; RBF: 65.6 +/- 1.3 mm Hg; P less than 0.01). In the subautoregulatory range GFR and RBF decreased in a linerar fashion and ceased at 40 and 19 mm Hg, respectively. Between 160 mm Hg and 95 mm Hg (threshold pressure for renin release) PRAD remained unchanged; below threshold pressure PRAD increased steeply (average slope: 0.34 ng AI.ml-1.h-1.mm Hg-1) indicating that resting renin release may be doubled by a fall of RAP by only 3 mm Hg. At the "break-off point" of RBF-autoregulation (66 mm Hg) renin release was 10-fold higher than the resting level. It is concluded that under physiological conditions (normal sodium diet) GFR and RBF are perfectly autoregulated over a wide pressure range. Renin release remains suppressed until RAP falls below a well defined threshold pressure slightly below the animal's resting systemic pressure. RBF is maintained at significantly lower pressures than GFR, indicating that autoregulation of RBF also involves postglomerular vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of blocking the formation of endothelium-derived relaxing factor/nitric oxide (EDNO) on pressure-dependent renin release (RR) was studied in six conscious foxhounds with chronically implanted catheters in the abdominal aorta and the renal vein. Renal blood flow (RBF) was measured with an ultrasonic transit-time flowmeter. RR was determined by multiplying the renal venous-arterial plasma renin activity difference with renal plasma flow. Renal artery pressure (RAP) was reduced in steps by a pneumatic occluder placed around the suprarenal abdominal aorta. A dose of 1,000 mg NG-nitro-L-arginine methyl ester (L-NAME) was given as a bolus to inhibit EDNO formation. In response to L-NAME, RAP increased (98 +/- 3 vs. 128 +/- 3 mmHg; P < 0.05), heart rate decreased (88 +/- 7 vs. 51 +/- 5 beats/min; P < 0.05), RBF decreased (280 +/- 19 vs. 185 +/- 24 ml/min; P < 0.05), and RR decreased (62 +/- 11 vs. 28 +/- 7 U; P < 0.05), whereas glomerular filtration rate changed little (38 +/- 3 vs. 35 +/- 4 ml/min; not significant). Below roughly 90 mmHg, RR was considerably attenuated by L-NAME as RAP was reduced in steps. At the lowest RAP (50 mmHg) RR was 1,946 +/- 406 U during control vs. 697 +/- 179 U after L-NAME (P < 0.05). Thus L-NAME inhibited pressure-dependent RR. This was especially pronounced in the low-pressure range.

No abstract

The administration of corticosterone for 5 consecutive days to normal rats on a standard sodium intake induced negative sodium and water balance. These effects were opposite those observed under DOCA treatment. However, not only under DOCA but also under corticosterone treatment extracellular fluid volume (ECFV) and plasma volume (PV) increased, and blood pressure (BP) rose in parallel. Plasma renin and angiotensin II concentrations declined under the influence of both steroids. Plasma arginine vasopressin concentrations increased under DOCA, whereas they transiently decreased under corticosterone administration. These data suggest that the common mediator for BP elevation due to steroid excess would be an increase in ECFV and PV. The pathways by which this increase is achieved seem to be different. Under DOCA treatment ECFV and PV increased subsequent to renal sodium and water retention. Under corticosterone, however, sodium and water were shifted from intra- to extracellular compartments, and a fraction of this shifted sodium and water was conserved in extracellular space, most likely because corticosterone also affected renal sodium handling.