Differential modulation of tissue function and therapeutic potential of selective inhibitors of cyclic nucleotide phosphodiesterase isoenzymes

Article Abstract:

The selective inhibition of cyclic nucleotide phosphodiesterase isoenzymes (PDI) affects the cyclic nucleotide levels and promotes the modulation of tissue functions at different subcellular sites. This property makes PDI selective inhibitors such as 1-methyl-2-isobutyl-8-methoxyethyl xanthine and denbufylline useful in the determination of the effects of isoenzymes on cyclic nucleotide hydrolysis. Furthermore, these PDI selective inhibitors can be therapeutically employed in various illnesses such as congestive heart failure, asthma, central disorders and hypertension.

Isoenzymes, Phosphodiesterases

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An approach to the development of novel antihypertensive drugs: Potential role of sodium pump inhibitors

Article Abstract:

The search for the endogenous sodium pump inhibitor (SPI) is crucial to the understanding of hypertension and to the development of antihypertensive drugs. Researchers have identified the oubain-like compound, digoxin-like compound, cardenolide-lipid conjugates and bufodienolide SPIs as possible regulators of blood pressure in humans and mammals. These compounds are believed to regulate sodium reabsorption by the kidney which leads to hypertension. Animal studies support the theory that SPI contributes to the development of hypertension.

Hypertension, Drug therapy

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Handy and Moore reply

Article Abstract:

The enzyme inhibitor 7-nitroindazole does not affect the endothelium-dependent relaxation of the blood vessels or increase in systemic blood pressure in anaesthetized rats contrary to claims. It was not mentioned that the observed vascular effects were concentrated only in the peripheral and central nervous systems and does not affect systemic blood pressure. The vascular effect of 7-NI is limited to the central nervous system and is attributed to the inhibition of neuronal nitric oxide formation.

Research, Blood vessels, Physiological regulation, Biological control systems

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