Antihypertensive effects of CS-045 treatment in obese Zucker rats

Rosiglitazone Restores G-Protein Coupling, Recruitment, and Function of Renal Dopamine D 1A Receptor in Obese Zucker Rats

“…Similar to obese control rats, basal UF and U Na V were significantly greater in obese treated rats, even though rosiglitazone treatment reduces blood pressure in these animals. This could be explained by the fact that thiozolidinedione derivates have been shown to increase U Na V. 20 Attenuated natriuretic and diuretic response to SKF-38393 in obese control rats could be partly owing to inability of dopamine and D 1A receptor agonist to inhibit sodium transporters in proximal tubules. This may result from (1) reduced abundance of D 1A receptors on the plasma membrane, (2) impaired coupling of D 1A receptors to G proteins, and, subsequently, (3) impaired dopamine-induced recruitment of D 1A receptors to the plasma membrane in obese rats.…”

Troglitazone inhibits angiotensin II‐induced DNA synthesis and migration in vascular smooth muscle cells

“…This potent effect of troglitazone on All-induced signalling might contribute to the observed in vivo effects of troglitazone to prevent neointimal hyperplasia in the injured vessel and to lower blood pressure in some animal models of hypertension. Tro and related thiazolidinediones have been shown to attenuate hypertension an a variety of animal models [15,16]. As insulin sensitizers these agents could lower blood pressure indirectly by improving insulin resistance [17].…”

Evidence against a role of insulin in hypertension in spontaneously hypertensive rats. CS-045 does not lower blood pressure despite improvement of insulin resistance.

“…Key Words • insulin resistance • rats, inbred SHR • thiazoles • blood pressure underlying metabolic derangements but also hypertension. In fact, drugs such as ciglitazone 10 and CS-045 (troglitazone) 11 have been reported to decrease blood pressure in the obese Zucker rat. The present study was therefore designed to test whether or not insulin resistance and hyperinsulinemia contribute to hypertension in spontaneously hypertensive rats (SHR, a model of human essential hypertension), which also have been reported to have glucose intolerance, hyperinsulinemia, and hence, insulin resistance.…”

“…- 11 In both studies, the drugs were administered for 4 to 8 weeks. The doses of CS-045 administered were about 15 and 67 mg/kg per day, the latter tending to lower blood pressure as early as 1 week after the start of treatment and producing a significant decrease in blood pressure after 6 weeks that was associated with marked natriuresis despite a lack of any difference in body weight.…”