Method of inducing vasorelaxation to treat pulmonary hypertensio

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

Patent

Rate now

  [ 0.00 ] – not rated yet Voters 0   Comments 0

Details

514 47, 514261, 514264, 514740, 514851, C07H 19167, C07H 1920, A01N 4390

Patent

active

059689110

DESCRIPTION:

BRIEF SUMMARY
Throughout this application, various references are referred to within parentheses or by arabic numberals. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Where not given in the text, full bibliographic citations for these references may be found at the end of each section, preceding the claims.


BACKGROUND OF THE INVENTION

Pulmonary hypertension is associated with significant morbidity and mortality, yet therapeutic options remain limited because agents which lower pulmonary vascular resistance (PVR) also lower systemic vascular resistance (SVR) (1). Nitric oxide (NO) gas has recently been shown to selectively lower PVR in pulmonary hypertension (2,3), but concerns remain involving its potential chromosomal effects (4), formation of toxic products from reaction with oxygen (4,5), logistic difficulties associated with delivery of a gas, and its short biological half-life, necessitating constant administration for continued effect (3,6).
Initial observations dealing with the use of cAMP and cGMP compounds go back to models of heart transplantation, where it was demonstrated that these systems were dysfunctional in the blood vessels of a transplanted heart. Supplementation of either the cGMP or the cAMP pathways could enhance the function of blood vessels within the graft, promoting successful transplantation. Stimulators of cAMP pathway used in these experiments included Sp-cAMPs, 8-Br-cAMP, db-cAMP, and phosphodiesterase inhibitors (indolidan, rolipram), all of which helped graft preservation. An antagonist of this pathway (RpcAMPS) blocked the beneficial effects of 8-Br-cAMP.
Nitric oxide is formed by cells lining blood vessels from the amino acid L-arginine, and leads to the formation of cGMP in the nearby cells. In the transplantation model, compounds which give off NO (nitroglycerin, nitroprusside), the NO precursor L-arginine, or 8-Br-cGMP (which acts like native cGMP but is capable of passing through cell membranes and therefore getting into cells) similarly benefitted heart preservation.
Both pathways (cAMP and cGMP) seemed to be dysfunctional in the setting of transplantation because of their roles in maintaining proper blood vessel function. Beneficial effects included improving blood flow, reducing damaging white blood cell infiltrations into blood vessels, preventing blood vessel leakiness, and preventing blood clot formation. The basis for these effects have been described in numerous basic science papers elsewhere, in which the roles of these compounds on these functions had been studied. Experiments performed in the context of lung transplantation indicated that these same beneficial effects were found in the blood vessels of the lungs.


SUMMARY OF THE INVENTION

This invention provides a method of decreasing pulmonary vascular resistance in a subject which comprises administering endotracheally or endobronchially an effective amount of a drug selected from the group consisting of cyclic nucleotides, phosphodiesterase inhibitors, nitric oxide precursors, nitric oxide donors, and nitric oxide analogs, thereby decreasing pulmonary vascular resistance.
This invention provides a method of selectively decreasing pulmonary vascular resistance in a subject which comprises administering endotracheally or endobronchially an effective amount of a drug selected from the group consisting of cyclic nucleotides, phosphodiesterase inhibitors, nitric oxide precursors, nitric oxide donors, and nitric oxide analogs, thereby decreasing pulmonary vascular resistance.


DESCRIPTION OF THE FIGURES

FIGS. 1A-1C: Establishment of pulmonary hypertension in three porcine models. (A) The thromboxane (Tx) A.sub.2 analog 9,11-dideoxy-11.alpha.,9.alpha.-epoxymethanoprostaglandin F.sub.2.alpha. was infused intravenously (n=9) initially at 0.1 .mu.g/kg/min, and titered until a stable mean PA pressure of 30 mmHg was reached, after which no dosage adjustments were made. Bar graphs r

REFERENCES:
patent: 4623666 (1986-11-01), Kennedy
patent: 4956348 (1990-09-01), Gilbard
patent: 5175151 (1992-12-01), Afonso et al.
patent: 5217997 (1993-06-01), Levere et al.
patent: 5250700 (1993-10-01), Bagli et al.
patent: 5362747 (1994-11-01), Cowart et al.
patent: 5366977 (1994-11-01), Pollard et al.
patent: 5370989 (1994-12-01), Stern et al.
patent: 5376666 (1994-12-01), Duncia
A.G. Gilman, et al., "Goodman and Gilman's The Pharmacological Basis of Therapeutics", Published 1980 by Macmillan Publishing Co., Inc. (N.Y.)592-607 Archer, et al. J. Appl. Physiol. (1990) 68(2):735-747.
Brackett, et al., Biochemical Pharmacology (1990) 39(12):1897-1904.
Lawson, et al., abstract presented at American Heart Association Meeting, Atlanta, Georgia, Nov. 8-11, 1993; and Rossaint, et al. The New England Journal of Medicine (Feb. 11, 1993) 328(6):399-405.

LandOfFree

Say what you really think

Search LandOfFree.com for the USA inventors and patents. Rate them and share your experience with other people.

Rating

Method of inducing vasorelaxation to treat pulmonary hypertensio does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Method of inducing vasorelaxation to treat pulmonary hypertensio, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of inducing vasorelaxation to treat pulmonary hypertensio will most certainly appreciate the feedback.

Rate now

     

Profile ID: LFUS-PAI-O-2055464

  Search
All data on this website is collected from public sources. Our data reflects the most accurate information available at the time of publication.