Hypertension research : official journal of the Japanese Society of Hypertension
-
Hyperosmolality in the renal medullary interstitium is generated by the renal countercurrent multiplication system, in which the medullary thick ascending limb (MAL) and the outer medullary collecting duct (OMCD) primarily participate. Since arginine vasopressin (AVP) regulates Na-K-ATPase activity directly via protein kinase A and indirectly via hyperosmolality, we investigated the acute and chronic effects of hyperosmolality on Na-K-ATPase and AVP-dependent cAMP generation in the MAL and OMCD. Microdissected MAL and OMCD from control and dehydrated rats were used for the measurement of Na-K-ATPase activity, mRNA expression of alpha-1, beta-1, and beta-2 subunits of Na-K-ATPase, and AVP-dependent cAMP generation. ⋯ Higher levels of AVP-dependent cAMP were generated in the MAL from dehydrated rats than that of controls, although incubation in hypertonic medium did not lead to additional increases in AVP-dependent cAMP accumulation. In contrast, AVP-dependent cAMP generation in the OMCD was stimulated by dehydration, and was further stimulated by incubation in hypertonic medium. These findings demonstrate that Na-K-ATPase is upregulated short- and long-term hyperosmolality in the MAL, but not in OMCD.
-
Patients with malignant hypertension sometimes exhibit microangiopathic hemolytic anemia/thrombocytopenia known as thrombotic microangiopathy (TMA). On the other hand, severe hypertension is sometimes associated with hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP). Because the clinical features of the two entities overlap significantly, it is sometimes difficult to distinguish one from the other. ⋯ Although both of our patients had severe hypertension with TMA, different therapeutic strategies ameliorated their illness: symptomatic treatment was effective in case 1, which showed normal ADAMTS13 activity, whereas plasma infusion was necessary to save case 2, which showed low ADAMTS13 activity. Thus, patients with a low level of ADAMTS13 activity might respond well to plasmapheresis or plasma infusion. When presented with patients with severe hypertension and thrombotic microangiopathy, ADAMTS13 activity may prove to be a promising adjunctive tool in differentiating TTP from TMA due to other etiologies, but in the meantime, we should make the choice of whether or not to perform plasmapheresis based on the degree of thrombocytopenia.
-
Clinical Trial
Vitamin C improves attenuated angiotensin II-induced endothelium-dependent vasodilation in human forearm vessels.
Endothelial dysfunction might be related to an increase in superoxide anion production in patients with hypertension, hypercholesterolemia, diabetes mellitus, and heart failure. Studies in animal models indicate that angiotensin II increases superoxide anion production by vascular tissues. We examined whether angiotensin II attenuates endothelium-dependent vasodilation via an increase in superoxide anion production in human forearm vessels in vivo. ⋯ The forearm vasodilator response to acetylcholine did not change during infusion of norepinephrine (n=3), which reduced forearm blood flow to a degree similar to that by angiotensin II infusion. These results suggest that angiotensin II attenuates endothelium-dependent forearm vasodilation, and vitamin C improves this impairment. Thus, angiotensin II likely attenuates endothelium-dependent vasodilation via an increase of superoxide anion production in the human forearm in vivo.
-
Recent studies have demonstrated that the activation of protein kinase Akt attenuates myocardial ischemia/reperfusion injury. However, it remains unknown whether adrenomedullin (AM), which is also a potent Akt activator, has cardioprotective effects after ischemia/reperfusion. In the present study, Sprague-Dawley rats were exposed to a 30-min period of ischemia induced by ligation of the left coronary artery followed by 24-h reperfusion. ⋯ AM significantly increased LV fractional shortening (23 +/- 2 vs. 28 +/- 2%, p < 0.05), and significantly reduced LV diastolic dimension (7.4 +/- 0.1 to 6.9 +/- 0.1 mm, p < 0.05) and myocardial infarct size (33 +/- 2 to 20 +/- 2%, p < 0.01) 4 weeks after ischemia/reperfusion. In conclusion, AM infusion during ischemia/reperfusion attenuated the development of LV remodeling and myocardial fibrosis in rats. Based on these results, the cardioprotective effects of AM may be attributed at least partly to its anti-apoptotic effect.
-
Randomized Controlled Trial Clinical Trial
Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy.
Combined antihypertensive therapy plays a crucial role in achieving targeted blood pressure reductions and renoprotection. We therefore compared the antihypertensive and antiproteinuric effects of combined therapy with either a calcium channel blocker (CCB) plus an angiotensin II receptor blocker (ARB) or an angiotensin converting enzyme inhibitor (ACE-I) plus an ARB in patients with type 2 diabetes mellitus complicated by overt nephropathy and mild to moderate hypertension. After a 12-week dietary control period, diabetic patients with mildly to moderately impaired renal function were randomly assigned to either a CCB (amlodipine 5 mg once daily) or an ACE-I (temocapril 2 mg once daily) for 12 weeks (monotherapy period). ⋯ Although the latter combination had a more profound effect, it was associated with an increased serum potassium concentration and worsening of renal anemia. Thus, the combination of a CCB and an ARB should be the first line antihypertensive therapy in those with overt diabetic nephropathy. The long-term efficacy of these combined antihypertensive therapies will need to be further addressed in a future study.