Cardiovascular Effects of a Renin Inhibitor in Relation to Posture in Nonhuman Primates

Pals, Donald T.; Degraaf, Garry L.; Kati, Warren M.; Lawson, Judy A.; Smith, Clark W.; Skala, Gerald

doi:10.3109/10641968509074757

Cited by 5 publications

(2 citation statements)

References 17 publications

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“…H 1 antagonists have been shown to inhibit increases in plasma renin activity during upright tilt ( 13 ). Although our data showed marked inhibition of both plasma renin activity and aldosterone, this cannot explain the 100% presyncope rate in the current study, as blockade of the renin-angiotensin-aldosterone system does not cause orthostatic hypotension if sympathetic responses are intact ( 16 ). Consider the effects of promethazine which might affect the sympathetic nervous system.…”

Section: Discussionmentioning

confidence: 58%

Effects of Promethazine and Midodrine on Orthostatic Tolerance

Shi¹,

Platts²,

Meck³

2011

aviat space environ med

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Section: Discussionmentioning

confidence: 58%

Effects of Promethazine and Midodrine on Orthostatic Tolerance

Shi¹,

Platts²,

Meck³

2011

aviat space environ med

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“…In a salt-depleted, low-renin hypertensive patient, a similar infusion of RIP gave a rapid drop in BP to undetectable levels (and lowered HR), while administration of captopriI gave a moderate and gradual fa11.246,259 Interestingly, no profound hypotension was seen for infusions of RIP (2 mg/kg/min) in either sodium-depleted or sodium-replete cynomolgus monkeys, regardless of posture. 260 H-142 (2-8) was studied in nine male volunteers. Infusions of H-142 into sodium-deficient humans (1 or 2.5 mg/kg/h) produced only a slight lowering of systolic BP, but a clear decrease in diastolic BP.…”

Section: F Renin Inhibitors In Humansmentioning

confidence: 99%

Renin inhibitors

Greenlee

1990

Medicinal Research Reviews

284

139

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Since the early 1980s, an intensive effort has been focused on the development of orally effective and long-acting inhibitors of renin. During this time, in vitro potency has increased greatly, with several transition-state inhibitor designs yielding inhibitors with subnanomolar IC50 values. In the meantime, both the molecular weight and peptide character of the inhibitors has decreased as important binding elements have been focused into smaller and more stable structures. The resulting inhibitors have shown promising activities in several in vivo models and (in two cases) in man. Nevertheless, renin inhibitors reported to date have limited oral bioavailability and short duration of action, and improvements in both will be necessary for them to compete effectively with ACE inhibitors. Renin inhibitors which have entered clinical studies have at least one naturally occurring amino acid and three or more amide bonds. It is reasonable to expect that continued development will produce wholly nonpeptide inhibitors with still lower MW, and it may be these "second-generation" inhibitors which will succeed as therapeutic agents. Development of orally effective and long-acting inhibitors of renin will enable their long-term antihypertensive efficacy and possible advantages over ACE inhibitor to be investigated.

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