PubMed · 13732018
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I H PAGE, F M BUMPUS. 1961. Angiotensin.. https://doi.org/10.1152/physrev.1961.41.2.331
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AIMS/HYPOTHESIS: This study aimed to identify the expression of angiotensin II receptors in isolated human islets and beta cells and to examine the functional consequences of their activation. MATERIALS AND METHODS: Single-cell RT-PCR was used to identify whether human islet cells express mRNA for type 1 angiotensin II receptors (AT(1)), and western blotting was used to determine AT(1) protein expression by human islets and MIN6 beta cells. We measured changes in intracellular calcium by microfluorimetry using Fura 2-loaded MIN6 cells and human islet cells. Dynamic insulin secretory responses were determined by RIA following perifusion of human islets and MIN6 cells. RESULTS: Human islets expressed mRNAs for both the angiotensin precursor, angiotensinogen, and for angiotensin-converting enzyme. In addition, human and mouse beta cells expressed AT(1). These were functionally coupled to increases in intracellular calcium, which occurred at least in part through phospholipase-C-sensitive mechanisms and calcium influx through voltage-operated calcium channels. Short-term exposure of human islets and MIN6 cells to angiotensin II caused a rapid, short-lived initiation of insulin secretion at 2 mmol/l glucose and potentiation of insulin secretion induced by glucose (at 8 and 16.7 mmol/l). CONCLUSIONS/INTERPRETATION: These data demonstrate that the AT(1) is expressed by beta cells and that angiotensin II effects a short-lived and direct stimulation of human and mouse beta cells to promote insulin secretion, most probably through elevations in intracellular calcium. Locally produced angiotensin II may be important in regulating a coordinated insulin secretory response from beta cells.
Sufficient O(2)-supply to the brain is necessary for an adequate cerebral energy metabolism, function and growth. To elucidate the relation between changes in, respectively, mean arterial blood pressure (MABP) and cerebral O(2)-supply and changes in the oxygenation state of hemoglobin during hypotension in preterm born lambs. Preterm lambs were delivered at 141 days (n=7) or 127 days (n=7) of gestation. Hypotension was induced by stepwise withdrawal of blood. Cerebral arterial blood gases were analyzed at the end of each level to calculate cerebral O(2)-supply. Near-infrared spectroscopy was used to measure changes in the concentration of cerebral oxyhemoglobin (cO(2)Hb), deoxyhemoglobin (cHHb) and cHbD (the difference between cO(2)Hb and cHHb). In the 141 and the 127 d lambs, changes in MABP and cerebral O(2)-supply were positively linearly related with DeltacO(2)Hb, and negatively with DeltacHHb. MABP was positively linearly related with changes in cHbD. During hemorrhagic hypotension, changes in MABP and cerebral O(2)-supply are reflected by changes in the oxygenation state of cerebral hemoglobin in near-term born lambs.
The present study investigated the action of des-aspartate-angiotensin I (DAA-I) on the pressor action of angiotensin II in the renal and mesenteric vasculature of WKY, SHR and streptozotocin (STZ)-induced diabetic rats. Angiotensin II-induced a dose-dependent pressor response in the renal vasculature. Compared to the WKY, the pressor response was enhanced in the SHR and reduced in the STZ-induced diabetic rat. DAA-I attenuated the angiotensin II pressor action in renal vasculature of WKY and SHR. The attenuation was observed for DAA-I concentration as low as 10(-18) M and was more prominent in SHR. However, the ability of DAA-I to reduce angiotensin II response was lost in the STZ-induced diabetic kidney. Instead, enhancement of angiotensin II pressor response was seen at the lower doses of the octapeptide. The effect of DAA-I was not inhibited by PD123319, an AT2 receptor antagonist, and indomethacin, a cyclo-oxygenase inhibitor in both WKY and SHR, indicating that its action was not mediated by angiotensin AT2 receptor and prostaglandins. The pressor responses to angiotensin II in mesenteric vascular bed were also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses were significantly smaller in SHR but no significant difference was observed between STZ-induced diabetic and WKY rat. Similarly, PD123319 and indomethacin had no effect on the action of DAA-I. The findings reiterate a regulatory role for DAA-I in vascular bed of the kidney and mesentery. By being active at circulating level, DAA-I subserves a physiological role. This function appears to be present in animals with diseased state of hypertension and diabetes. It is likely that DAA-I functions are modified to accommodate the ongoing vascular remodeling.