Atrial natriuretic factor (ANF) and nitric oxide (NO) stimulate production of guanosine 3′,5′-cyclic monophosphate (cGMP) and are natriuretic. Split-drop micropuncture was performed on anesthetized rats to determine the effects of ANF and the NO donor sodium nitroprusside (SNP) on proximal tubular fluid absorption rate ( J va). Compared with control solutions, SNP (10−4 M) decreased J va by 23% when administered luminally and by 35% when added to the peritubular perfusate. Stimulation of fluid uptake by luminal angiotensin II (ANG II; 10−9 M) was abolished by SNP (10−4 and 10−6 M). In proximal tubule suspensions, ANF (10−6 M) increased cGMP concentration to 143%, whereas SNP (10−6, 10−5, 10−4, 10−3 M) raised cGMP to 231, 594, 687, and 880%, respectively. S-nitroso- N-acetylpenicillamine (SNAP) also raised cGMP concentrations with similar dose-response relations. These studies demonstrate inhibition by luminal and peritubular NO of basal and ANG II-stimulated proximal fluid absorption in vivo. The ability of SNP to inhibit basal fluid uptake whereas ANF only affected ANG II-stimulated transport may be because of production of higher concentrations of cGMP by SNP.

In autoradiographic studies in anesthetized rats, 125I-labeled amylin binding was associated with proximal convoluted tubules but not distal tubules, interstitium, or glomeruli in the renal cortex. Split-drop micropuncture experiments showed that perfusion of the peritubular capillaries with amylin (10(-9) M) stimulated proximal tubular fluid absorption by 28%. This effect was inhibited by luminal addition of ethylisopropylamiloride, indicating mediation by a brush-border Na+/H+ exchanger. Intravenous infusion of an amylin binding antagonist, AC-187, reduced proximal fluid reabsorption (22%) in anesthetized rats, indicating a role for endogenous amylin in salt homeostasis. In primary cultures of rat proximal tubule cells, amylin (10(-7) M) stimulated proliferation with a potency equal to epidermal growth factor. Peptide antagonists (AC-187, AC-413, and AC-512) of the amylin binding sites in the renal cortex blocked the mitogenic action of amylin. We conclude that amylin acts on renal proximal tubules to promote sodium and water reabsorption and cell proliferation. These novel actions may have implications for the development of hypertension for example in non-insulin-dependent diabetes mellitus and obesity in which hyperamylinemia has been observed.

Intravenous infusion of either camboginol or morelloflavone from Garcinia dulcis (GD) exerted diuretic, hypotensive, and vasorelaxant effects in either normotensive or hypertensive rats. This study aims to investigate the effects of GD flower extract on arterial blood pressure (ABP) and renal excretory functions. Male Wistar rats (8-weekold) were divided into 4 groups (group I-IV, n = 6 each) in both acute and sub-chronic protocols. The GD extract was orally administrated to group II-IV at the dose of 50, 100, or 200 mg/kg, respectively, while group I served as vehicle control. The oral administration was performed before the experiment in acute protocol and daily for 2 weeks in the sub-chronic protocol. The ABP and renal excretory functions were measured in the anesthetized rats. The levels of fasting blood glucose (FBG), plasma lipid profiles, and liver enzymes were evaluated in the sub-chronic experiment along with liver histology. The results showed that acute administration of GD extract significantly decreased ABP but increased renal blood flow, glomerular filtration rate, urine flow rate, osmolar clearance, and negative free water clearance when compared with the control. In the sub-chronic protocol, the GD extract significantly decreased ABP but did not alter the renal excretory functions. The plasma levels of FBG, lipid profiles, liver enzymes, and the histology of liver were not changed. It is concluded that acute oral administration of GD extract possessed hypotensive and diuretic effects whereas the sub-chronic treatment of GD showed hypotensive effect and no alterations in liver function, FBG, and plasma lipid profiles.

Morelloflavone, a biflavonoid from Southeast Asian folk medical plant Garcinia dulcis, possesses powerful antioxidant activity both in vivo and in vitro. We aimed to evaluate the hypotensive and diuretic effect of morelloflavone in two-kidneysone-clip (2K1C)

The hexane insoluble fraction of the Garcinia dulcis (GD) flower extract comprises mainly camboginol and morelloflavone which possess potent in vivo and in vitro antioxidant properties. This study aimed to evaluate the effects of 4-week oral administration of GD flower extract on the arterial blood pressure (ABP) and the excretory function of the kidney in the 2-kidneys-1-clip (2K1C) renovascular hypertensive rats (total=12) compared to sham operated (SO) normotensive Wistar rats (total=12). Four weeks after hypertensive-induced surgery, either 50 mg/kg BW GD flower extract or vehicle was orally administered to the 2K1C or SO groups (n=6/group) daily for four weeks. ABP and the renal excretory function were studied in anesthetized rats, and expression of endothelial nitric oxide synthase (eNOS) mRNA in the isolated thoracic aorta were measured. In the 2K1C rats, GD flower extract significantly decreased ABP while increased significantly eNOS mRNA levels. GD flower extract did not exert a diuretic effect in either SO and 2K1C rats since there was no change in observed urine excretion, but it did tend to attenuated the renal tubular damage caused by renovascular hypertension. GD flower extract was anti-hypertensive in this model of renovascular hypertension and problably acts via the endothelial nitric oxide signaling pathway.